Chapter 15 : Bacterial Evasion of Host Antimicrobial Peptide Defenses

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Bacterial Evasion of Host Antimicrobial Peptide Defenses, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819286/9781555819279_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555819286/9781555819279_Chap15-2.gif


Antimicrobial peptides (AMPs) are small (<10 kDa) soluble host defense peptides that play an important role in the mammalian innate immune response, helping to prevent infection by inhibiting pathogen growth on skin and mucosal surfaces and subsequent dissemination to normally sterile sites. These natural antibiotics are produced by many cell types including epithelial cells, leukocytes (neutrophils, macrophages, dendritic cells, and mast cells), platelets, endothelial cells, and adipocytes in response to tissue damage or infectious stimuli and are found in body fluids and secretions including saliva, urine, sweat, and breast milk. To date, more than 2,000 AMPs have been identified from a wide variety of organisms including bacteria, insects, plants, amphibians, birds, reptiles, and mammals including humans ( ). Whereas prokaryotic AMPs are produced as a competitive strategy to facilitate the acquisition of nutrients and promote niche colonization ( ), AMPs produced by higher organisms are generally conceived to carry out immune defense functions. In humans, the principal AMPs are hydrophobic molecules composed of ∼10 to 50 amino acid residues with a net positive charge, which exhibit varying degrees of broad-spectrum bioactivity against Gram-positive and Gram-negative bacteria, fungi, protozoan parasites, and certain enveloped viruses ( ). AMPs may be expressed constitutively or induced in response to infection (e.g., proinflammatory cytokines, toll-like receptor [TLR] signaling) ( ) and are commonly produced as propeptides that undergo subsequent proteolytic processing to the mature bioactive peptide ( ). AMPs with central roles in host defense are active at micromolar to nanomolar concentrations and facilitate microbial killing through perturbation of the cytoplasmic membrane ( ). Several important human pathogens display significant resistance to AMPs, which appears to play a key role in their potential to produce serious invasive infections.

Citation: Cole J, Nizet V. 2016. Bacterial Evasion of Host Antimicrobial Peptide Defenses, p 413-443. In Kudva I, Cornick N, Plummer P, Zhang Q, Nicholson T, Bannantine J, Bellaire B (ed),

Virulence Mechanisms of Bacterial Pathogens, Fifth Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0006-2015
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Schematic representation of the multiple resistance mechanisms developed by bacteria to overcome host antimicrobial peptides. Modification of the bacterial outer membrane. Bacterial resistance to cationic antimicrobial peptides is mediated by alterations in surface charge. Gram-positive bacteria: -alanine modification of cell wall teichoic acid (), -lysine (), or -alanine modification of phosphatidylglycerol (). Gram-negative bacteria: aminoarabinose or acylation modifications of lipid A in LPS (), or addition of ethanolamine to lipid A (). The increased positive charge on bacterial surface repels cationic AMPs. Shielding of the bacterial surface through the trapping and inactivation of AMPs in the extracellular milieu enhances resistance and pathogenicity. Surface-associated capsule traps AMP (e.g., operon), surface protein binds AMP (e.g., GAS M1 protein, GBS PilB pilus protein), secreted protein binds AMP (e.g., GAS SIC protein or staphylokinase), or bacterial proteases release host proteoglycans to block AMP (e.g., LasA). Membrane efflux pumps function by translocating the AMP out of the cell (e.g., spp. Mtr, Typhimurium Sap, QacA, and spp. VraFG). Degradation and inactivation of AMPs by bacterial proteases (e.g., GAS streptococcal pyrogenic exotoxin B protease, SepA, Typhimurium PgtE, aureolysin and V8 protease, elastase, and gelatinase). Bacterial exposure to AMPs upregulates the expression of AMP-resistance genes through global gene regulatory networks (e.g., Typhimurium and PhoPQ and PmrAB). Alteration of host processes by bacteria, including the downregulation of host AMP production (e.g., spp. transcriptional factor MxiE) or the upregulation and activation of host AMP-degrading proteases (e.g., ). Abbreviations: om, bacterial outer membrane; im, bacterial inner membrane.

Citation: Cole J, Nizet V. 2016. Bacterial Evasion of Host Antimicrobial Peptide Defenses, p 413-443. In Kudva I, Cornick N, Plummer P, Zhang Q, Nicholson T, Bannantine J, Bellaire B (ed),

Virulence Mechanisms of Bacterial Pathogens, Fifth Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0006-2015
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Steckbeck JD,, Deslouches B,, Montelaro RC . 2014. Antimicrobial peptides: new drugs for bad bugs? Expert Opin Biol Ther 14 : 11 14.[PubMed] [CrossRef]
2. Di Francesco A,, Favaroni A,, Donati M . 2013. Host defense peptides: general overview and an update on their activity against Chlamydia spp. Expert Rev Anti Infect Ther 11 : 1215 1224.[PubMed] [CrossRef]
3. Anaya-Lopez JL,, Lopez-Meza JE,, Ochoa-Zarzosa A . 2013. Bacterial resistance to cationic antimicrobial peptides. Crit Rev Microbiol 39 : 180 195.[PubMed] [CrossRef]
4. Jenssen H,, Hamill P,, Hancock RE . 2006. Peptide antimicrobial agents. Clin Microbiol Rev 19 : 491 511.[PubMed] [CrossRef]
5. Nakatsuji T,, Gallo RL . 2012. Antimicrobial peptides: old molecules with new ideas. J Invest Dermatol 132 : 887 895.[PubMed] [CrossRef]
6. Pinheiro da Silva F,, Machado MC . 2012. Antimicrobial peptides: clinical relevance and therapeutic implications. Peptides 36 : 308 314.[PubMed] [CrossRef]
7. Morrison G,, Kilanowski F,, Davidson D,, Dorin J . 2002. Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect Immun 70 : 3053 3060.[PubMed] [CrossRef]
8. Guralp SA,, Murgha YE,, Rouillard JM,, Gulari E . 2013. From design to screening: a new antimicrobial peptide discovery pipeline. PLoS One 8 : e59305. doi:10.1371/journal.pone.0059305. [PubMed] [CrossRef]
9. Nguyen LT,, Haney EF,, Vogel HJ . 2011. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 29 : 464 472.[PubMed] [CrossRef]
10. Lehrer RI,, Ganz T . 2002. Cathelicidins: a family of endogenous antimicrobial peptides. Curr Opin Hematol 9 : 18 22.[PubMed] [CrossRef]
11. Ganz T . 2003. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 3 : 710 720.[PubMed] [CrossRef]
12. Ayabe T,, Satchell DP,, Wilson CL,, Parks WC,, Selsted ME,, Ouellette AJ . 2000. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 1 : 113 118.[PubMed] [CrossRef]
13. Yount NY,, Yeaman MR . 2013. Peptide antimicrobials: cell wall as a bacterial target. Ann N Y Acad Sci 1277 : 127 138.[PubMed] [CrossRef]
14. Ganz T,, Lehrer RI . 1997. Antimicrobial peptides of leukocytes. Curr Opin Hematol 4 : 53 58.[PubMed] [CrossRef]
15. Jones DE,, Bevins CL . 1992. Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 267 : 23216 23225.[PubMed]
16. Quayle AJ,, Porter EM,, Nussbaum AA,, Wang YM,, Brabec C,, Yip KP,, Mok SC . 1998. Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 152 : 1247 1258.[PubMed]
17. Duits LA,, Ravensbergen B,, Rademaker M,, Hiemstra PS,, Nibbering PH . 2002. Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cells. Immunology 106 : 517 525.[PubMed] [CrossRef]
18. Kosciuczuk EM,, Lisowski P,, Jarczak J,, Strzalkowska N,, Jozwik A,, Horbanczuk J,, Krzyzewski J,, Zwierzchowski L,, Bagnicka E . 2012. Cathelicidins: family of antimicrobial peptides. A review. Mol Biol Rep 39 : 10957 10970.[PubMed] [CrossRef]
19. Yeaman MR . 2010. Platelets in defense against bacterial pathogens. Cell Mol Life Sci 67 : 525 544.[PubMed] [CrossRef]
20. Koprivnjak T,, Peschel A . 2011. Bacterial resistance mechanisms against host defense peptides. Cell Mol Life Sci 68 : 2243 2254.[PubMed] [CrossRef]
21. Kwakman PH,, Krijgsveld J,, de Boer L,, Nguyen LT,, Boszhard L,, Vreede J,, Dekker HL,, Speijer D,, Drijfhout JW,, te Velde AA,, Crielaard W,, Vogel HJ,, Vandenbroucke-Grauls CM,, Zaat SA . 2011. Native thrombocidin-1 and unfolded thrombocidin-1 exert antimicrobial activity via distinct structural elements. J Biol Chem 286 : 43506 43514.[PubMed] [CrossRef]
22. Zasloff M . 2002. Antimicrobial peptides of multicellular organisms. Nature 415 : 389 395.[PubMed] [CrossRef]
23. Senyurek I,, Paulmann M,, Sinnberg T,, Kalbacher H,, Deeg M,, Gutsmann T,, Hermes M,, Kohler T,, Gotz F,, Wolz C,, Peschel A,, Schittek B . 2009. Dermcidin-derived peptides show a different mode of action than the cathelicidin LL-37 against Staphylococcus aureus . Antimicrob Agents Chemother 53 : 2499 2509.[PubMed] [CrossRef]
24. Gennaro R,, Zanetti M . 2000. Structural features and biological activities of the cathelicidin-derived antimicrobial peptides. Biopolymers 55 : 31 49.[PubMed] [CrossRef]
25. Yeaman MR,, Yount NY . 2003. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55 : 27 55.[PubMed] [CrossRef]
26. Ehrenstein G,, Lecar H . 1977. Electrically gated ionic channels in lipid bilayers. Q Rev Biophys 10 : 1 34.[PubMed] [CrossRef]
27. Matsuzaki K,, Murase O,, Fujii N,, Miyajima K . 1996. An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation. Biochemistry 35 : 11361 11368.[PubMed] [CrossRef]
28. Pietiainen M,, Francois P,, Hyyrylainen HL,, Tangomo M,, Sass V,, Sahl HG,, Schrenzel J,, Kontinen VP . 2009. Transcriptome analysis of the responses of S taphylococcus aureus to antimicrobial peptides and characterization of the roles of vraDE and vraSR in antimicrobial resistance. BMC Genomics 10 : 429. [PubMed] [CrossRef]
29. Straus SK,, Hancock RE . 2006. Mode of action of the new antibiotic for Gram-positive pathogens daptomycin: comparison with cationic antimicrobial peptides and lipopeptides. Biochim Biophys Acta 1758 : 1215 1223.[PubMed] [CrossRef]
30. Brogden KA . 2005. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3 : 238 250.[PubMed] [CrossRef]
31. Muller A,, Ulm H,, Reder-Christ K,, Sahl HG,, Schneider T . 2012. Interaction of type A lantibiotics with undecaprenol-bound cell envelope precursors. Microb Drug Resist 18 : 261 270.[PubMed] [CrossRef]
32. Islam MR,, Nagao J,, Zendo T,, Sonomoto K . 2012. Antimicrobial mechanism of lantibiotics. Biochem Soc Trans 40 : 1528 1533.[PubMed] [CrossRef]
33. Cho JH,, Sung BH,, Kim SC . 2009. Buforins: histone H2A-derived antimicrobial peptides from toad stomach. Biochim Biophys Acta 1788 : 1564 1569.[PubMed] [CrossRef]
34. Subbalakshmi C,, Sitaram N . 1998. Mechanism of antimicrobial action of indolicidin. FEMS Microbiol Lett 160 : 91 96.[PubMed] [CrossRef]
35. Haney EF,, Petersen AP,, Lau CK,, Jing W,, Storey DG,, Vogel HJ . 2013. Mechanism of action of puroindoline derived tryptophan-rich antimicrobial peptides. Biochim Biophys Acta 1828 : 1802 1813.[PubMed] [CrossRef]
36. Lehrer RI,, Barton A,, Daher KA,, Harwig SS,, Ganz T,, Selsted ME . 1989. Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest 84 : 553 561.[PubMed] [CrossRef]
37. Di Nardo A,, Vitiello A,, Gallo RL . 2003. Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol 170 : 2274 2278.[PubMed] [CrossRef]
38. Nizet V,, Ohtake T,, Lauth X,, Trowbridge J,, Rudisill J,, Dorschner RA,, Pestonjamasp V,, Piraino J,, Huttner K,, Gallo RL . 2001. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414 : 454 457.[PubMed] [CrossRef]
39. Rosenberger CM,, Gallo RL,, Finlay BB . 2004. Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci USA 101 : 2422 2427.[PubMed] [CrossRef]
40. Chromek M,, Slamova Z,, Bergman P,, Kovacs L,, Podracka L,, Ehren I,, Hokfelt T,, Gudmundsson GH,, Gallo RL,, Agerberth B,, Brauner A . 2006. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12 : 636 641.[PubMed] [CrossRef]
41. Bergman P,, Johansson L,, Wan H,, Jones A,, Gallo RL,, Gudmundsson GH,, Hokfelt T,, Jonsson AB,, Agerberth B . 2006. Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection. Infect Immun 74 : 6982 6991.[PubMed] [CrossRef]
42. Kumar A,, Gao N,, Standiford TJ,, Gallo RL,, Yu FS . 2010. Topical flagellin protects the injured corneas from Pseudomonas aeruginosa infection. Microbes Infect 12 : 978 989.[PubMed] [CrossRef]
43. Kovach MA,, Ballinger MN,, Newstead MW,, Zeng X,, Bhan U,, Yu FS,, Moore BB,, Gallo RL,, Standiford TJ . 2012. Cathelicidin-related antimicrobial peptide is required for effective lung mucosal immunity in Gram-negative bacterial pneumonia. J Immunol 189 : 304 311.[PubMed] [CrossRef]
44. Augustin DK,, Heimer SR,, Tam C,, Li WY,, Le Due JM,, Evans DJ,, Fleiszig SM . 2011. Role of defensins in corneal epithelial barrier function against Pseudomonas aeruginosa traversal. Infect Immun 79 : 595 605.[PubMed] [CrossRef]
45. Kolar SS,, Baidouri H,, Hanlon S,, McDermott AM . 2013. Protective role of murine beta-defensins 3 and 4 and cathelin-related antimicrobial peptide in Fusarium solani keratitis. Infect Immun 81 : 2669 2677.[PubMed] [CrossRef]
46. Lee PH,, Ohtake T,, Zaiou M,, Murakami M,, Rudisill JA,, Lin KH,, Gallo RL . 2005. Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection. Proc Natl Acad Sci USA 102 : 3750 3755.[PubMed] [CrossRef]
47. Salzman NH,, Ghosh D,, Huttner KM,, Paterson Y,, Bevins CL . 2003. Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422 : 522 526.[PubMed] [CrossRef]
48. Niyonsaba F,, Ushio H,, Nakano N,, Ng W,, Sayama K,, Hashimoto K,, Nagaoka I,, Okumura K,, Ogawa H . 2007. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 127 : 594 604.[PubMed] [CrossRef]
49. Zanetti M . 2004. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 75 : 39 48.[PubMed] [CrossRef]
50. Koczulla R,, von Degenfeld G,, Kupatt C,, Krotz F,, Zahler S,, Gloe T,, Issbrucker K,, Unterberger P,, Zaiou M,, Lebherz C,, Karl A,, Raake P,, Pfosser A,, Boekstegers P,, Welsch U,, Hiemstra PS,, Vogelmeier C,, Gallo RL,, Clauss M,, Bals R . 2003. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111 : 1665 1672.[PubMed] [CrossRef]
51. Elssner A,, Duncan M,, Gavrilin M,, Wewers MD . 2004. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J Immunol 172 : 4987 4994.[PubMed] [CrossRef]
52. Davidson DJ,, Currie AJ,, Reid GS,, Bowdish DM,, MacDonald KL,, Ma RC,, Hancock RE,, Speert DP . 2004. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J Immunol 172 : 1146 1156.[PubMed] [CrossRef]
53. Territo MC,, Ganz T,, Selsted ME,, Lehrer R . 1989. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 84 : 2017 2020.[PubMed] [CrossRef]
54. Kurosaka K,, Chen Q,, Yarovinsky F,, Oppenheim JJ,, Yang D . 2005. Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant. J Immunol 174 : 6257 6265.[PubMed] [CrossRef]
55. Niyonsaba F,, Iwabuchi K,, Someya A,, Hirata M,, Matsuda H,, Ogawa H,, Nagaoka I . 2002. A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology 106 : 20 26.[PubMed] [CrossRef]
56. Niyonsaba F,, Someya A,, Hirata M,, Ogawa H,, Nagaoka I . 2001. Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D(2) production from mast cells. Eur J Immunol 31 : 1066 1075.[PubMed] [CrossRef]
57. Lohner K . 2009. New strategies for novel antibiotics: peptides targeting bacterial cell membranes. Gen Physiol Biophys 28 : 105 116.[PubMed] [CrossRef]
58. Gutsmann T,, Hagge SO,, Larrick JW,, Seydel U,, Wiese A . 2001. Interaction of CAP18-derived peptides with membranes made from endotoxins or phospholipids. Biophys J 80 : 2935 2945.[CrossRef]
59. Oren Z,, Lerman JC,, Gudmundsson GH,, Agerberth B,, Shai Y . 1999. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. Biochem J 341 : 501 513.[PubMed] [CrossRef]
60. Schmidtchen A,, Pasupuleti M,, Malmsten M . 2014. Effect of hydrophobic modifications in antimicrobial peptides. Adv Colloid Interface Sci 205 : 265 274.[PubMed] [CrossRef]
61. Guilhelmelli F,, Vilela N,, Albuquerque P,, Derengowski L da S,, Silva-Pereira I,, Kyaw CM . 2013. Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and of bacterial resistance. Front Microbiol 4 : 353. [PubMed] [CrossRef]
62. Raetz CR,, Reynolds CM,, Trent MS,, Bishop RE . 2007. Lipid A modification systems in Gram-negative bacteria. Annu Rev Biochem 76 : 295 329.[PubMed] [CrossRef]
63. Guo L,, Lim KB,, Poduje CM,, Daniel M,, Gunn JS,, Hackett M,, Miller SI . 1998. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell 95 : 189 198.[PubMed] [CrossRef]
64. Brown S,, Santa Maria JP Jr,, Walker S . 2013. Wall teichoic acids of Gram-positive bacteria. Annu Rev Microbiol 67 : 313 336.[PubMed] [CrossRef]
65. Neuhaus FC,, Baddiley J . 2003. A continuum of anionic charge: structures and functions of d-alanyl-teichoic acids in Gram-positive bacteria. Microbiol Mol Biol Rev 67 : 686 723.[CrossRef]
66. Poyart C,, Pellegrini E,, Marceau M,, Baptista M,, Jaubert F,, Lamy MC,, Trieu-Cuot P . 2003. Attenuated virulence of Streptococcus agalactiae deficient in d-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. Mol Microbiol 49 : 1615 1625.[PubMed] [CrossRef]
67. Fabretti F,, Theilacker C,, Baldassarri L,, Kaczynski Z,, Kropec A,, Holst O,, Huebner J . 2006. Alanine esters of enterococcal lipoteichoic acid play a role in biofilm formation and resistance to antimicrobial peptides. Infect Immun 74 : 4164 4171.[PubMed] [CrossRef]
68. Kovacs M,, Halfmann A,, Fedtke I,, Heintz M,, Peschel A,, Vollmer W,, Hakenbeck R,, Bruckner R . 2006. A functional dlt operon, encoding proteins required for incorporation of d-alanine in teichoic acids in Gram-positive bacteria, confers resistance to cationic antimicrobial peptides in Streptococcus pneumoniae . J Bacteriol 188 : 5797 5805.[PubMed] [CrossRef]
69. Morath S,, Geyer A,, Hartung T . 2001. Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus . J Exp Med 193 : 393 397.[PubMed] [CrossRef]
70. Grangette C,, Nutten S,, Palumbo E,, Morath S,, Hermann C,, Dewulf J,, Pot B,, Hartung T,, Hols P,, Mercenier A . 2005. Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids. Proc Natl Acad Sci USA 102 : 10321 10326.[PubMed] [CrossRef]
71. Kristian SA,, Datta V,, Weidenmaier C,, Kansal R,, Fedtke I,, Peschel A,, Gallo RL,, Nizet V . 2005. d-alanylation of teichoic acids promotes group A Streptococcus antimicrobial peptide resistance, neutrophil survival, and epithelial cell invasion. J Bacteriol 187 : 6719 6725.[PubMed] [CrossRef]
72. Peschel A,, Otto M,, Jack RW,, Kalbacher H,, Jung G,, Gotz F . 1999. Inactivation of the dlt operon in Staphylococcus aureus confers sensitivity to defensins, protegrins, and other antimicrobial peptides. J Biol Chem 274 : 8405 8410.[PubMed] [CrossRef]
73. Andra J,, Goldmann T,, Ernst CM,, Peschel A,, Gutsmann T . 2011. Multiple peptide resistance factor (MprF)-mediated resistance of Staphylococcus aureus against antimicrobial peptides coincides with a modulated peptide interaction with artificial membranes comprising lysyl-phosphatidylglycerol. J Biol Chem 286 : 18692 18700.[PubMed] [CrossRef]
74. Peschel A . 2002. How do bacteria resist human antimicrobial peptides? Trends Microbiol 10 : 179 186.[PubMed] [CrossRef]
75. Kristian SA,, Lauth X,, Nizet V,, Goetz F,, Neumeister B,, Peschel A,, Landmann R . 2003. Alanylation of teichoic acids protects Staphylococcus aureus against Toll-like receptor 2-dependent host defense in a mouse tissue cage infection model. J Infect Dis 188 : 414 423.[PubMed] [CrossRef]
76. Heptinstall S,, Archibald AR,, Baddiley J . 1970. Teichoic acids and membrane function in bacteria. Nature 225 : 519 521.[PubMed] [CrossRef]
77. MacArthur AE,, Archibald AR . 1984. Effect of culture pH on the pere-alanine ester content of lipoteichoic acid in Staphylococcus aureus . J Bacteriol 160 : 792 793.[PubMed]
78. Perego M,, Glaser P,, Minutello A,, Strauch MA,, Leopold K,, Fischer W . 1995. Incorporation of d-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation. J Biol Chem 270 : 15598 15606.[PubMed] [CrossRef]
79. Poyart C,, Lamy MC,, Boumaila C,, Fiedler F,, Trieu-Cuot P . 2001. Regulation of d-alanyl-lipoteichoic acid biosynthesis in Streptococcus agalactiae involves a novel two-component regulatory system. J Bacteriol 183 : 6324 6334.[PubMed] [CrossRef]
80. Saar-Dover R,, Bitler A,, Nezer R,, Shmuel-Galia L,, Firon A,, Shimoni E,, Trieu-Cuot P,, Shai Y . 2012. d-alanylation of lipoteichoic acids confers resistance to cationic peptides in group B Streptococcus by increasing the cell wall density. PLoS Pathog 8 : e1002891. doi:10.1371/journal.ppat.1002891. [PubMed] [CrossRef]
81. Kristian SA,, Durr M,, Van Strijp JA,, Neumeister B,, Peschel A . 2003. MprF-mediated lysinylation of phospholipids in Staphylococcus aureus leads to protection against oxygen-independent neutrophil killing. Infect Immun 71 : 546 549.[PubMed] [CrossRef]
82. Peschel A,, Jack RW,, Otto M,, Collins LV,, Staubitz P,, Nicholson G,, Kalbacher H,, Nieuwenhuizen WF,, Jung G,, Tarkowski A,, van Kessel KP,, van Strijp JA . 2001. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J Exp Med 193 : 1067 1076.[PubMed] [CrossRef]
83. Abachin E,, Poyart C,, Pellegrini E,, Milohanic E,, Fiedler F,, Berche P,, Trieu-Cuot P . 2002. Formation of d-alanyl-lipoteichoic acid is required for adhesion and virulence of Listeria monocytogenes . Mol Microbiol 43 : 1 14.[PubMed] [CrossRef]
84. Walter J,, Loach DM,, Alqumber M,, Rockel C,, Hermann C,, Pfitzenmaier M,, Tannock GW . 2007. d-alanyl ester depletion of teichoic acids in Lactobacillus reuteri 100-23 results in impaired colonization of the mouse gastrointestinal tract. Environ Microbiol 9 : 1750 1760.[PubMed] [CrossRef]
85. Ernst CM,, Staubitz P,, Mishra NN,, Yang SJ,, Hornig G,, Kalbacher H,, Bayer AS,, Kraus D,, Peschel A . 2009. The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion. PLoS Pathog 5 : e1000660. doi:10.1371/journal.ppat.1000660. [PubMed] [CrossRef]
86. Staubitz P,, Neumann H,, Schneider T,, Wiedemann I,, Peschel A . 2004. MprF-mediated biosynthesis of lysylphosphatidylglycerol, an important determinant in staphylococcal defensin resistance. FEMS Microbiol Lett 231 : 67 71.[PubMed] [CrossRef]
87. Nishi H,, Komatsuzawa H,, Fujiwara T,, McCallum N,, Sugai M . 2004. Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus . Antimicrob Agents Chemother 48 : 4800 4807.[PubMed] [CrossRef]
88. Izadpanah A,, Gallo RL . 2005. Antimicrobial peptides. J Am Acad Dermatol 52 : 381 390; quiz 391–392.[PubMed] [CrossRef]
89. Nawrocki KL,, Crispell EK,, McBride SM . 2014. Antimicrobial peptide resistance mechanisms of Gram-positive bacteria. Antibiotics 3 : 461 492.[PubMed] [CrossRef]
90. Roy H,, Ibba M . 2008. RNA-dependent lipid remodeling by bacterial multiple peptide resistance factors. Proc Natl Acad Sci USA 105 : 4667 4672.[PubMed] [CrossRef]
91. Maloney E,, Stankowska D,, Zhang J,, Fol M,, Cheng QJ,, Lun S,, Bishai WR,, Rajagopalan M,, Chatterjee D,, Madiraju MV . 2009. The two-domain LysX protein of Mycobacterium tuberculosis is required for production of lysinylated phosphatidylglycerol and resistance to cationic antimicrobial peptides. PLoS Pathog 5 : e1000534. doi:10.1371/journal.ppat.1000534. [PubMed] [CrossRef]
92. Maloney E,, Lun S,, Stankowska D,, Guo H,, Rajagoapalan M,, Bishai WR,, Madiraju MV . 2011. Alterations in phospholipid catabolism in Mycobacterium tuberculosis lysX mutant. Front Microbiol 2 : 19. [PubMed] [CrossRef]
93. Thedieck K,, Hain T,, Mohamed W,, Tindall BJ,, Nimtz M,, Chakraborty T,, Wehland J,, Jansch L . 2006. The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes . Mol Microbiol 62 : 1325 1339.[PubMed] [CrossRef]
94. Klein S,, Lorenzo C,, Hoffmann S,, Walther JM,, Storbeck S,, Piekarski T,, Tindall BJ,, Wray V,, Nimtz M,, Moser J . 2009. Adaptation of Pseudomonas aeruginosa to various conditions includes tRNA-dependent formation of alanyl-phosphatidylglycerol. Mol Microbiol 71 : 551 565.[PubMed] [CrossRef]
95. Samant S,, Hsu FF,, Neyfakh AA,, Lee H . 2009. The Bacillus anthracis protein MprF is required for synthesis of lysylphosphatidylglycerols and for resistance to cationic antimicrobial peptides. J Bacteriol 191 : 1311 1319.[PubMed] [CrossRef]
96. Hamilton A,, Popham DL,, Carl DJ,, Lauth X,, Nizet V,, Jones AL . 2006. Penicillin-binding protein 1a promotes resistance of group B Streptococcus to antimicrobial peptides. Infect Immun 74 : 6179 6187.[PubMed] [CrossRef]
97. West NP,, Jungnitz H,, Fitter JT,, McArthur JD,, Guzman CA,, Walker MJ . 2000. Role of phosphoglucomutase of Bordetella bronchiseptica in lipopolysaccharide biosynthesis and virulence. Infect Immun 68 : 4673 4680.[PubMed] [CrossRef]
98. Buchanan JT,, Stannard JA,, Lauth X,, Ostland VE,, Powell HC,, Westerman ME,, Nizet V . 2005. Streptococcus iniae phosphoglucomutase is a virulence factor and a target for vaccine development. Infect Immun 73 : 6935 6944.[PubMed] [CrossRef]
99. Gao LY,, Laval F,, Lawson EH,, Groger RK,, Woodruff A,, Morisaki JH,, Cox JS,, Daffe M,, Brown EJ . 2003. Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol Microbiol 49 : 1547 1563.[PubMed] [CrossRef]
100. Gunn JS,, Ryan SS,, Van Velkinburgh JC,, Ernst RK,, Miller SI . 2000. Genetic and functional analysis of a PmrA-PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar Typhimurium. Infect Immun 68 : 6139 6146.[PubMed] [CrossRef]
101. Tamayo R,, Choudhury B,, Septer A,, Merighi M,, Carlson R,, Gunn JS . 2005. Identification of cptA, a PmrA-regulated locus required for phosphoethanolamine modification of the Salmonella enterica serovar Typhimurium lipopolysaccharide core. J Bacteriol 187 : 3391 3399.[PubMed] [CrossRef]
102. Gunn JS . 2001. Bacterial modification of LPS and resistance to antimicrobial peptides. J Endotoxin Res 7 : 57 62.[PubMed] [CrossRef]
103. McCoy AJ,, Liu H,, Falla TJ,, Gunn JS . 2001. Identification of Proteus mirabilis mutants with increased sensitivity to antimicrobial peptides. Antimicrob Agents Chemother 45 : 2030 2037.[PubMed] [CrossRef]
104. Marceau M,, Sebbane F,, Collyn F,, Simonet M . 2003. Function and regulation of the Salmonella-like pmrF antimicrobial peptide resistance operon in Yersinia pseudotuberculosis . Adv Exp Med Biol 529 : 253 256.[PubMed] [CrossRef]
105. Cheng HY,, Chen YF,, Peng HL . 2010. Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43. J Biomed Sci 17 : 60. [PubMed] [CrossRef]
106. Moskowitz SM,, Ernst RK,, Miller SI . 2004. PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol 186 : 575 579.[PubMed] [CrossRef]
107. Ernst RK,, Yi EC,, Guo L,, Lim KB,, Burns JL,, Hackett M,, Miller SI . 1999. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa . Science 286 : 1561 1565.[PubMed] [CrossRef]
108. Tran AX,, Whittimore JD,, Wyrick PB,, McGrath SC,, Cotter RJ,, Trent MS . 2006. The lipid A 1-phosphatase of Helicobacter pylori is required for resistance to the antimicrobial peptide polymyxin. J Bacteriol 188 : 4531 4541.[PubMed] [CrossRef]
109. Cullen TW,, Giles DK,, Wolf LN,, Ecobichon C,, Boneca IG,, Trent MS . 2011. Helicobacter pylori versus the host: remodeling of the bacterial outer membrane is required for survival in the gastric mucosa. PLoS Pathog 7 : e1002454. doi:10.1371/journal.ppat.1002454. [PubMed] [CrossRef]
110. Lewis LA,, Choudhury B,, Balthazar JT,, Martin LE,, Ram S,, Rice PA,, Stephens DS,, Carlson R,, Shafer WM . 2009. Phosphoethanolamine substitution of lipid A and resistance of Neisseria gonorrhoeae to cationic antimicrobial peptides and complement-mediated killing by normal human serum. Infect Immun 77 : 1112 1120.[PubMed] [CrossRef]
111. Tzeng YL,, Ambrose KD,, Zughaier S,, Zhou X,, Miller YK,, Shafer WM,, Stephens DS . 2005. Cationic antimicrobial peptide resistance in Neisseria meningitidis . J Bacteriol 187 : 5387 5396.[PubMed] [CrossRef]
112. Albiger B,, Johansson L,, Jonsson AB . 2003. Lipooligosaccharide-deficient Neisseria meningitidis shows altered pilus-associated characteristics. Infect Immun 71 : 155 162.[PubMed] [CrossRef]
113. Jones A,, Georg M,, Maudsdotter L,, Jonsson AB . 2009. Endotoxin, capsule, and bacterial attachment contribute to Neisseria meningitidis resistance to the human antimicrobial peptide LL-37. J Bacteriol 191 : 3861 3868.[PubMed] [CrossRef]
114. Keo T,, Collins J,, Kunwar P,, Blaser MJ,, Iovine NM . 2011. Campylobacter capsule and lipooligosaccharide confer resistance to serum and cationic antimicrobials. Virulence 2 : 30 40.[PubMed] [CrossRef]
115. Naito M,, Frirdich E,, Fields JA,, Pryjma M,, Li J,, Cameron A,, Gilbert M,, Thompson SA,, Gaynor EC . 2010. Effects of sequential Campylobacter jejuni 81-176 lipooligosaccharide core truncations on biofilm formation, stress survival, and pathogenesis. J Bacteriol 192 : 2182 2192.[PubMed] [CrossRef]
116. Bishop RE,, Gibbons HS,, Guina T,, Trent MS,, Miller SI,, Raetz CR . 2000. Transfer of palmitate from phospholipids to lipid A in outer membranes of Gram-negative bacteria. EMBO J 19 : 5071 5080.[PubMed] [CrossRef]
117. Robey M,, O’Connell W,, Cianciotto NP . 2001. Identification of Legionella pneumophilarcp, a pagP-like gene that confers resistance to cationic antimicrobial peptides and promotes intracellular infection. Infect Immun 69 : 4276 4286.[PubMed] [CrossRef]
118. Starner TD,, Swords WE,, Apicella MA,, McCray PB Jr . 2002. Susceptibility of nontypeable Haemophilus influenzae to human beta-defensins is influenced by lipooligosaccharide acylation. Infect Immun 70 : 5287 5289.[PubMed] [CrossRef]
119. Lysenko ES,, Gould J,, Bals R,, Wilson JM,, Weiser JN . 2000. Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect Immun 68 : 1664 1671.[PubMed] [CrossRef]
120. Clements A,, Tull D,, Jenney AW,, Farn JL,, Kim SH,, Bishop RE,, McPhee JB,, Hancock RE,, Hartland EL,, Pearse MJ,, Wijburg OL,, Jackson DC,, McConville MJ,, Strugnell RA . 2007. Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides. J Biol Chem 282 : 15569 15577.[PubMed] [CrossRef]
121. Matson JS,, Yoo HJ,, Hakansson K,, Dirita VJ . 2010. Polymyxin B resistance in El Tor Vibrio cholerae requires lipid acylation catalyzed by MsbB. J Bacteriol 192 : 2044 2052.[PubMed] [CrossRef]
122. Braff MH,, Jones AL,, Skerrett SJ,, Rubens CE . 2007. Staphylococcus aureus exploits cathelicidin antimicrobial peptides produced during early pneumonia to promote staphylokinase-dependent fibrinolysis. J Infect Dis 195 : 1365 1372.[PubMed] [CrossRef]
123. Jin T,, Bokarewa M,, Foster T,, Mitchell J,, Higgins J,, Tarkowski A . 2004. Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J Immunol 172 : 1169 1176.[PubMed] [CrossRef]
124. Frick IM,, Akesson P,, Rasmussen M,, Schmidtchen A,, Bjorck L . 2003. SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J Biol Chem 278 : 16561 16566.[PubMed] [CrossRef]
125. Pence MA,, Rooijakkers SH,, Cogen AL,, Cole JN,, Hollands A,, Gallo RL,, Nizet V . 2010. Streptococcal inhibitor of complement promotes innate immune resistance phenotypes of invasive M1T1 group A Streptococcus . J Innate Immun 2 : 587 595.[PubMed] [CrossRef]
126. Fernie-King BA,, Seilly DJ,, Davies A,, Lachmann PJ . 2002. Streptococcal inhibitor of complement inhibits two additional components of the mucosal innate immune system: secretory leukocyte proteinase inhibitor and lysozyme. Infect Immun 70 : 4908 4916.[PubMed] [CrossRef]
127. Walker MJ,, Barnett TC,, McArthur JD,, Cole JN,, Gillen CM,, Henningham A,, Sriprakash KS,, Sanderson-Smith ML,, Nizet V . 2014. Disease manifestations and pathogenic mechanisms of group A Streptococcus . Clin Microbiol Rev 27 : 264 301.[PubMed] [CrossRef]
128. Cole JN,, Barnett TC,, Nizet V,, Walker MJ . 2011. Molecular insight into invasive group A streptococcal disease. Nat Rev Microbiol 9 : 724 736.[PubMed] [CrossRef]
129. Steer AC,, Law I,, Matatolu L,, Beall BW,, Carapetis JR . 2009. Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis 9 : 611 616.[PubMed] [CrossRef]
130. Lauth X,, von Kockritz-Blickwede M,, McNamara CW,, Myskowski S,, Zinkernagel AS,, Beall B,, Ghosh P,, Gallo RL,, Nizet V . 2009. M1 protein allows group A streptococcal survival in phagocyte extracellular traps through cathelicidin inhibition. J Innate Immun 1 : 202 214.[PubMed] [CrossRef]
131. Jones AL,, Mertz RH,, Carl DJ,, Rubens CE . 2007. A streptococcal penicillin-binding protein is critical for resisting innate airway defenses in the neonatal lung. J Immunol 179 : 3196 3202.[PubMed] [CrossRef]
132. Maisey HC,, Quach D,, Hensler ME,, Liu GY,, Gallo RL,, Nizet V,, Doran KS . 2008. A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence. FASEB J 22 : 1715 1724.[PubMed] [CrossRef]
133. Lancefield RC . 1928. The antigenic complex of Streptococcus haemolyticus. I. Demonstration of a type-specific substance in extracts of Streptococcus haemolyticus . J Exp Med 47 : 91 103.[PubMed] [CrossRef]
134. McCarty M . 1952. The lysis of group A hemolytic streptococci by extracellular enzymes of Streptomyces albus. II. Nature of the cellular substrate attacked by the lytic enzymes. J Exp Med 96 : 569 580.[PubMed] [CrossRef]
135. van Sorge NM,, Cole JN,, Kuipers K,, Henningham A,, Aziz RK,, Kasirer-Friede A,, Lin L,, Berends ET,, Davies MR,, Dougan G,, Zhang F,, Dahesh S,, Shaw L,, Gin J,, Cunningham M,, Merriman JA,, Hutter J,, Lepenies B,, Rooijakkers SH,, Malley R,, Walker MJ,, Shattil SJ,, Schlievert PM,, Choudhury B,, Nizet V . 2014. The classical lancefield antigen of group A Streptococcus is a virulence determinant with implications for vaccine design. Cell Host Microbe 15 : 729 740.[PubMed] [CrossRef]
136. Schmidtchen A,, Frick IM,, Bjorck L . 2001. Dermatan sulphate is released by proteinases of common pathogenic bacteria and inactivates antibacterial alpha-defensin. Mol Microbiol 39 : 708 713.[PubMed] [CrossRef]
137. Park PW,, Pier GB,, Preston MJ,, Goldberger O,, Fitzgerald ML,, Bernfield M . 2000. Syndecan-1 shedding is enhanced by LasA, a secreted virulence factor of Pseudomonas aeruginosa . J Biol Chem 275 : 3057 3064.[PubMed] [CrossRef]
138. Heilmann C,, Schweitzer O,, Gerke C,, Vanittanakom N,, Mack D,, Gotz F . 1996. Molecular basis of intercellular adhesion in the biofilm-forming Staphylococcus epidermidis . Mol Microbiol 20 : 1083 1091.[PubMed] [CrossRef]
139. Vuong C,, Kocianova S,, Voyich JM,, Yao Y,, Fischer ER,, DeLeo FR,, Otto M . 2004. A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J Biol Chem 279 : 54881 54886.[PubMed] [CrossRef]
140. Vuong C,, Voyich JM,, Fischer ER,, Braughton KR,, Whitney AR,, DeLeo FR,, Otto M . 2004. Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system. Cell Microbiol 6 : 269 275.[PubMed] [CrossRef]
141. Kocianova S,, Vuong C,, Yao Y,, Voyich JM,, Fischer ER,, DeLeo FR,, Otto M . 2005. Key role of poly-gamma-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis . J Clin Invest 115 : 688 694.[PubMed] [CrossRef]
142. Cole JN,, Pence MA,, von Kockritz-Blickwede M,, Hollands A,, Gallo RL,, Walker MJ,, Nizet V . 2010. M protein and hyaluronic acid capsule are essential for in vivo selection of covRS mutations characteristic of invasive serotype M1T1 group A Streptococcus . mBio 1 : e00191-10. doi:10.1128/mBio.00191-10. [CrossRef]
143. Campos MA,, Vargas MA,, Regueiro V,, Llompart CM,, Alberti S,, Bengoechea JA . 2004. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun 72 : 7107 7114.[PubMed] [CrossRef]
144. Moranta D,, Regueiro V,, March C,, Llobet E,, Margareto J,, Larrarte E,, Garmendia J,, Bengoechea JA . 2010. Klebsiella pneumoniae capsule polysaccharide impedes the expression of beta-defensins by airway epithelial cells. Infect Immun 78 : 1135 1146.[PubMed] [CrossRef]
145. Llobet E,, Tomas JM,, Bengoechea JA . 2008. Capsule polysaccharide is a bacterial decoy for antimicrobial peptides. Microbiology 154 : 3877 3886.[PubMed] [CrossRef]
146. Spinosa MR,, Progida C,, Tala A,, Cogli L,, Alifano P,, Bucci C . 2007. The Neisseria meningitidis capsule is important for intracellular survival in human cells. Infect Immun 75 : 3594 3603.[PubMed] [CrossRef]
147. Chan C,, Burrows LL,, Deber CM . 2004. Helix induction in antimicrobial peptides by alginate in biofilms. J Biol Chem 279 : 38749 38754.[PubMed] [CrossRef]
148. Piddock LJ . 2006. Multidrug-resistance efflux pumps: not just for resistance. Nat Rev Microbiol 4 : 629 636.[PubMed] [CrossRef]
149. Davidson AL,, Dassa E,, Orelle C,, Chen J . 2008. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol Mol Biol Rev 72 : 317 364.[PubMed] [CrossRef]
150. Stein T,, Heinzmann S,, Solovieva I,, Entian KD . 2003. Function of Lactococcus lactis nisin immunity genes nisI and nisFEG after coordinated expression in the surrogate host Bacillus subtilis . J Biol Chem 278 : 89 94.[PubMed] [CrossRef]
151. Stein T,, Heinzmann S,, Dusterhus S,, Borchert S,, Entian KD . 2005. Expression and functional analysis of the subtilin immunity genes spaIFEG in the subtilin-sensitive host Bacillus subtilis MO1099. J Bacteriol 187 : 822 828.[PubMed] [CrossRef]
152. Suarez JM,, Edwards AN,, McBride SM . 2013. The Clostridium difficile cpr locus is regulated by a noncontiguous two-component system in response to type A and B lantibiotics. J Bacteriol 195 : 2621 2631.[PubMed] [CrossRef]
153. McBride SM,, Sonenshein AL . 2011. Identification of a genetic locus responsible for antimicrobial peptide resistance in Clostridium difficile . Infect Immun 79 : 167 176.[PubMed] [CrossRef]
154. Mascher T,, Margulis NG,, Wang T,, Ye RW,, Helmann JD . 2003. Cell wall stress responses in Bacillus subtilis: the regulatory network of the bacitracin stimulon. Mol Microbiol 50 : 1591 1604.[PubMed] [CrossRef]
155. Meehl M,, Herbert S,, Gotz F,, Cheung A . 2007. Interaction of the GraRS two-component system with the VraFG ABC transporter to support vancomycin-intermediate resistance in Staphylococcus aureus . Antimicrob Agents Chemother 51 : 2679 2689.[PubMed] [CrossRef]
156. Kramer NE,, van Hijum SA,, Knol J,, Kok J,, Kuipers OP . 2006. Transcriptome analysis reveals mechanisms by which Lactococcus lactis acquires nisin resistance. Antimicrob Agents Chemother 50 : 1753 1761.[PubMed] [CrossRef]
157. Majchrzykiewicz JA,, Kuipers OP,, Bijlsma JJ . 2010. Generic and specific adaptive responses of Streptococcus pneumoniae to challenge with three distinct antimicrobial peptides, bacitracin, LL-37, and nisin. Antimicrob Agents Chemother 54 : 440 451.[PubMed] [CrossRef]
158. Mandin P,, Fsihi H,, Dussurget O,, Vergassola M,, Milohanic E,, Toledo-Arana A,, Lasa I,, Johansson J,, Cossart P . 2005. VirR, a response regulator critical for Listeria monocytogenes virulence. Mol Microbiol 57 : 1367 1380.[PubMed] [CrossRef]
159. Podlesek Z,, Comino A,, Herzog-Velikonja B,, Zgur-Bertok D,, Komel R,, Grabnar M . 1995. Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Mol Microbiol 16 : 969 976.[PubMed] [CrossRef]
160. Manson JM,, Keis S,, Smith JM,, Cook GM . 2004. Acquired bacitracin resistance in Enterococcus faecalis is mediated by an ABC transporter and a novel regulatory protein, BcrR. Antimicrob Agents Chemother 48 : 3743 3748.[PubMed] [CrossRef]
161. Charlebois A,, Jalbert LA,, Harel J,, Masson L,, Archambault M . 2012. Characterization of genes encoding for acquired bacitracin resistance in Clostridium perfringens . PLoS One 7 : e44449. doi:10.1371/journal.pone.0044449. [PubMed] [CrossRef]
162. Tsuda H,, Yamashita Y,, Shibata Y,, Nakano Y,, Koga T . 2002. Genes involved in bacitracin resistance in Streptococcus mutans . Antimicrob Agents Chemother 46 : 3756 3764.[PubMed] [CrossRef]
163. Bengoechea JA,, Skurnik M . 2000. Temperature-regulated efflux pump/potassium antiporter system mediates resistance to cationic antimicrobial peptides in Yersinia . Mol Microbiol 37 : 67 80.[PubMed] [CrossRef]
164. Padilla E,, Llobet E,, Domenech-Sanchez A,, Martinez-Martinez L,, Bengoechea JA,, Alberti S . 2010. Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother 54 : 177 183.[PubMed] [CrossRef]
165. Zahner D,, Zhou X,, Chancey ST,, Pohl J,, Shafer WM,, Stephens DS . 2010. Human antimicrobial peptide LL-37 induces MefE/Mel-mediated macrolide resistance in Streptococcus pneumoniae . Antimicrob Agents Chemother 54 : 3516 3519.[PubMed] [CrossRef]
166. Chen YC,, Chuang YC,, Chang CC,, Jeang CL,, Chang MC . 2004. A K + uptake protein, TrkA, is required for serum, protamine, and polymyxin B resistance in Vibrio vulnificus . Infect Immun 72 : 629 636.[PubMed] [CrossRef]
167. Parra-Lopez C,, Lin R,, Aspedon A,, Groisman EA . 1994. A Salmonella protein that is required for resistance to antimicrobial peptides and transport of potassium. EMBO J 13 : 3964 3972.[PubMed]
168. Shafer WM,, Qu X,, Waring AJ,, Lehrer RI . 1998. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc Natl Acad Sci USA 95 : 1829 1833.[PubMed] [CrossRef]
169. Veal WL,, Nicholas RA,, Shafer WM . 2002. Overexpression of the MtrC-MtrD-MtrE efflux pump due to an mtrR mutation is required for chromosomally mediated penicillin resistance in Neisseria gonorrhoeae . J Bacteriol 184 : 5619 5624.[PubMed] [CrossRef]
170. Jerse AE,, Sharma ND,, Simms AN,, Crow ET,, Snyder LA,, Shafer WM . 2003. A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection. Infect Immun 71 : 5576 5582.[PubMed] [CrossRef]
171. Rinker SD,, Trombley MP,, Gu X,, Fortney KR,, Bauer ME . 2011. Deletion of mtrC in Haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the CpxRA regulon. Infect Immun 79 : 2324 2334.[PubMed] [CrossRef]
172. Mason KM,, Munson RS Jr,, Bakaletz LO . 2005. A mutation in the sap operon attenuates survival of nontypeable Haemophilus influenzae in a chinchilla model of otitis media. Infect Immun 73 : 599 608.[PubMed] [CrossRef]
173. Parra-Lopez C,, Baer MT,, Groisman EA . 1993. Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium . EMBO J 12 : 4053 4062.[PubMed]
174. Mount KL,, Townsend CA,, Rinker SD,, Gu X,, Fortney KR,, Zwickl BW,, Janowicz DM,, Spinola SM,, Katz BP,, Bauer ME . 2010. Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans. Infect Immun 78 : 1176 1184.[PubMed] [CrossRef]
175. Eswarappa SM,, Panguluri KK,, Hensel M,, Chakravortty D . 2008. The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence. Microbiology 154 : 666 678.[PubMed] [CrossRef]
176. Saidijam M,, Benedetti G,, Ren Q,, Xu Z,, Hoyle CJ,, Palmer SL,, Ward A,, Bettaney KE,, Szakonyi G,, Meuller J,, Morrison S,, Pos MK,, Butaye P,, Walravens K,, Langton K,, Herbert RB,, Skurray RA,, Paulsen IT,, O’Reilly J,, Rutherford NG,, Brown MH,, Bill RM,, Henderson PJ . 2006. Microbial drug efflux proteins of the major facilitator superfamily. Curr Drug Targets 7 : 793 811.[PubMed] [CrossRef]
177. Kupferwasser LI,, Skurray RA,, Brown MH,, Firth N,, Yeaman MR,, Bayer AS . 1999. Plasmid-mediated resistance to thrombin-induced platelet microbicidal protein in staphylococci: role of the qacA locus. Antimicrob Agents Chemother 43 : 2395 2399.[PubMed]
178. Bayer AS,, Kupferwasser LI,, Brown MH,, Skurray RA,, Grkovic S,, Jones T,, Mukhopadhay K,, Yeaman MR . 2006. Low-level resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activity. Antimicrob Agents Chemother 50 : 2448 2454.[PubMed] [CrossRef]
179. Bayer AS,, Cheng D,, Yeaman MR,, Corey GR,, McClelland RS,, Harrel LJ,, Fowler VG Jr . 1998. In vitro resistance to thrombin-induced platelet microbicidal protein among clinical bacteremic isolates of Staphylococcus aureus correlates with an endovascular infectious source. Antimicrob Agents Chemother 42 : 3169 3172.[PubMed]
180. Shinnar AE,, Butler KL,, Park HJ . 2003. Cathelicidin family of antimicrobial peptides: proteolytic processing and protease resistance. Bioorg Chem 31 : 425 436.[PubMed] [CrossRef]
181. Schmidtchen A,, Frick IM,, Andersson E,, Tapper H,, Bjorck L . 2002. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol Microbiol 46 : 157 168.[PubMed] [CrossRef]
182. Johansson L,, Thulin P,, Sendi P,, Hertzen E,, Linder A,, Akesson P,, Low DE,, Agerberth B,, Norrby-Teglund A . 2008. Cathelicidin LL-37 in severe Streptococcus pyogenes soft tissue infections in humans. Infect Immun 76 : 3399 3404.[PubMed] [CrossRef]
183. Sieprawska-Lupa M,, Mydel P,, Krawczyk K,, Wojcik K,, Puklo M,, Lupa B,, Suder P,, Silberring J,, Reed M,, Pohl J,, Shafer W,, McAleese F,, Foster T,, Travis J,, Potempa J . 2004. Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother 48 : 4673 4679.[PubMed] [CrossRef]