Chapter 8 : Ecology and Evolution of Chromosomal Gene Transfer between Environmental Microorganisms and Pathogens

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

Preview this chapter:
Zoom in

Ecology and Evolution of Chromosomal Gene Transfer between Environmental Microorganisms and Pathogens, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819743/9781555819736_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555819743/9781555819736_Chap08-2.gif


The evolution of living beings is a complex process, with a large degree of serendipity, in which the offspring displace the ancestors. Indeed, what we find in the current multicellular world, and more specifically in the animal world, are the last members of an evolutionary process; all other members in the same branch of the phylogenetic tree have disappeared. In this regard, most multicellular organisms can be considered as newcomers on Earth, which have appeared quite recently in evolutionary terms. Although there are still some progenitors that stand after the evolution of their siblings, the most common scenario for multicellular organisms is that ancestors disappear once the evolved progeny displace them (see the evolution of ). This type of recent evolution followed by extinction is not so frequent in the case of bacterial species, although it may have happened on some occasions (see the example of described below). Indeed, the origin of different pathogens has been tracked to more than 100 million years ago, long before the human being (or an ancestor) was present on Earth ( ). Despite this extremely long evolutionary time, which should have allowed for large diversification with the loss of ancestors, bacterial core genomes are remarkably stable. It could be expected that the allelic variants of bacterial genes should cover nearly the entire potential spectrum of synonymous mutations and even those nonsynonymous mutations without substantial associated fitness costs. However, today we can use multilocus sequence typing for distinguishing among different clones in bacterial populations, under the assumption that, at least for several of the core genome genes, fixation of mutations is not a frequent event ( ). It then seems that, unless there is a major change in habitat, mutation-driven evolution is not the most important process in the speciation of bacteria in general, and in particular in the case of bacterial pathogens. A major force in such evolution, however, would be the acquisition of genetic elements ( ), what has been dubbed evolution in quantum leaps ( ). These acquired genes constitute the accessory genome of an organism and the pangenome of a given species ( ).

Citation: Martínez J. 2019. Ecology and Evolution of Chromosomal Gene Transfer between Environmental Microorganisms and Pathogens, p 141-160. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0006-2016
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Evolutionary trajectories of bacterial pathogens. (A) The process of speciation of a pathogen (larger circles) such as . This process usually begins with the acquisition, by HGT, of a set of genes (red circle) that allow the shift of the pathogen’s habitat from the environment to an infected host ( ). If the rate of transmission is high enough, the newborn pathogen will disseminate among different individuals ( ) and evolve by different mechanisms that include mutation and eventually genome reduction ( ). These evolutionary processes might cause the deadaptation of the pathogen to its original habitat, in which case the chances of the microorganism recolonizing natural ecosystems will be low ( ). Once the organism is a pathogen, it can change host specificity by acquiring novel genes ( ) and eventually by losing of determinants unneeded in the novel host ( ). In all cases, the integration of the acquired elements into the preformed bacterial metabolic and regulatory networks will be tuned by mutation. (B) The process of short-sighted evolution of opportunistic pathogens with an environmental origin, like . These microorganisms infect patients, presenting a basal disease, using virulence determinants already encoded in their genomes ( ). During chronic infection, the infective strain evolves mainly by mutation and genome rearrangements ( ). However, since it only infects people with a basal disease, transmission rates are usually low, which precludes clonal expansion and further diversification. Since adaptation to the new host is of no value for colonizing the environmental habitat ( ), this is a dead-end evolutionary process. (C) The evolution of pathogens such as that present virulence determinants with a dual role in the environment and for infections, in which case the colonization of one of these two habitats does not severely compromise the colonization of the other ( ). Reproduced with permission from reference .

Citation: Martínez J. 2019. Ecology and Evolution of Chromosomal Gene Transfer between Environmental Microorganisms and Pathogens, p 141-160. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0006-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Evolution of . The process of speciation from an environmental, nonpathogenic ancestor is a good example of the evolutionary steps that are involved in the emergence of bacterial pathogens. This process began with the acquisition of the plasmid pCD1 by environmental . This plasmid harbors genes encoding virulence determinants such as type III secretion systems and effector Yop proteins. From this ancestor of virulent species, two branches have evolved. One diverged through the acquisition of the stable toxin (Yst) and led to the speciation of . This species has further evolved through acquisition and loss of genes (not shown in this figure). The other branch diverged through the acquisition of the high pathogenicity island (HPI*), which encodes an iron-uptake system and is present as well in different , and by the incorporation of insecticidal genes. is a successful clone that emerged recently from through the acquisition of the plasmids pCP1, which encodes the plasminogen activator gene, and pMT1, which allows colonization of the gut of fleas. The loss of insect toxins is an important event for the persistence of in its insect vectors. The acquisition of insertion sequences is the basis of the genome rearrangements and gene loss of . Finally, the entire process of adaptation to a new host is modulated by the mutation-driven optimization of the regulatory and metabolic networks of the pathogen. This evolutionary process is described in more detail in references , and . Reproduced with permission from reference .

Citation: Martínez J. 2019. Ecology and Evolution of Chromosomal Gene Transfer between Environmental Microorganisms and Pathogens, p 141-160. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0006-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Exaptation and gene decontextualization in the evolution of antibiotic resistance. Antibiotic resistance genes () have evolved for millions of years located in the chromosomes of their original hosts (a). During this evolution, the expression of these determinants (R) from their promoters (P) has been finely tuned to respond to several signals that might include the response to environmental and metabolic changes (blue arrows). Besides, the determinants encoded by these genes are integrated in physiological networks, where they can play a role as metabolic enzymes. S1 to S3 represent metabolites of the same pathway, and A1 and B1 metabolites of other interconnected pathways. When these genes are integrated in gene capture (for instance, an integron) and transfer units (for instance, a plasmid), they can be transferred to a new host and submitted to strong antibiotic selective pressure (b), and they can be constitutively expressed from a strong promoter (P) present in the capture unit and therefore lack the regulatory and physiological network encountered in the original host (gene decontextualization). Under these circumstances, the only function these determinants can play is antibiotic resistance, in such a way that this functional shift is not the consequence of adaptive changes in the determinants but rather of changes in their environment (exaptation). Reproduced with permission from reference .

Citation: Martínez J. 2019. Ecology and Evolution of Chromosomal Gene Transfer between Environmental Microorganisms and Pathogens, p 141-160. In Baquero F, Bouza E, Gutiérrez-Fuentes J, Coque T (ed), Microbial Transmission. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MTBP-0006-2016
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ochman H,, Groisman EA . 1994. The origin and evolution of species differences in Escherichia coli and Salmonella typhimurium. EXS 69 : 479 493.[CrossRef]
2. Maiden MC,, Bygraves JA,, Feil E,, Morelli G,, Russell JE,, Urwin R,, Zhang Q,, Zhou J,, Zurth K,, Caugant DA,, Feavers IM,, Achtman M,, Spratt BG . 1998. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 95 : 3140 3145.[CrossRef]
3. Achtman M,, Wagner M . 2008. Microbial diversity and the genetic nature of microbial species. Nat Rev Microbiol 6 : 431 440.[CrossRef][PubMed]
4. Ochman H,, Lawrence JG,, Groisman EA . 2000. Lateral gene transfer and the nature of bacterial innovation. Nature 405 : 299 304.[CrossRef][PubMed]
5. Wiedenbeck J,, Cohan FM . 2011. Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. FEMS Microbiol Rev 35 : 957 976.[CrossRef][PubMed]
6. Groisman EA,, Ochman H . 1996. Pathogenicity islands: bacterial evolution in quantum leaps. Cell 87 : 791 794.[CrossRef][PubMed]
7. Rouli L,, Merhej V,, Fournier PE,, Raoult D . 2015. The bacterial pangenome as a new tool for analysing pathogenic bacteria. New Microbes New Infect 7 : 72 85.[CrossRef][PubMed]
8. Martínez JL . 2013. Bacterial pathogens: from natural ecosystems to human hosts. Environ Microbiol 15 : 325 333.[CrossRef][PubMed]
9. Martínez JL . 2008. Antibiotics and antibiotic resistance genes in natural environments. Science 321 : 365 367.[CrossRef][PubMed]
10. Martínez JL,, Baquero F,, Andersson DI . 2007. Predicting antibiotic resistance. Nat Rev Microbiol 5 : 958 965.[CrossRef][PubMed]
11. Martinez JL,, Fajardo A,, Garmendia L,, Hernandez A,, Linares JF,, Martínez-Solano L,, Sánchez MB . 2009. A global view of antibiotic resistance. FEMS Microbiol Rev 33 : 44 65.[CrossRef][PubMed]
12. Fajardo A,, Linares JF,, Martínez JL . 2009. Towards an ecological approach to antibiotics and antibiotic resistance genes. Clin Microbiol Infect 15( Suppl 1) : 14 16.[CrossRef][PubMed]
13. Lukjancenko O,, Wassenaar TM,, Ussery DW . 2010. Comparison of 61 sequenced Escherichia coli genomes. Microb Ecol 60 : 708 720.[CrossRef][PubMed]
14. Levin BR,, Bergstrom CT . 2000. Bacteria are different: observations, interpretations, speculations, and opinions about the mechanisms of adaptive evolution in prokaryotes. Proc Natl Acad Sci U S A 97 : 6981 6985.[CrossRef]
15. Hacker J,, Kaper JB . 2000. Pathogenicity islands and the evolution of microbes. Annu Rev Microbiol 54 : 641 679.[CrossRef][PubMed]
16. Berg G,, Martinez JL . 2015. Friends or foes: can we make a distinction between beneficial and harmful strains of the Stenotrophomonas maltophilia complex? Front Microbiol 6 : 241.[CrossRef][PubMed]
17. Alonso A,, Rojo F,, Martínez JL . 1999. Environmental and clinical isolates of Pseudomonas aeruginosa show pathogenic and biodegradative properties irrespective of their origin. Environ Microbiol 1 : 421 430.[CrossRef][PubMed]
18. Wiehlmann L,, Wagner G,, Cramer N,, Siebert B,, Gudowius P,, Morales G,, Köhler T,, van Delden C,, Weinel C,, Slickers P,, Tümmler B . 2007. Population structure of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 104 : 8101 8106.[CrossRef][PubMed]
19. Morales G,, Wiehlmann L,, Gudowius P,, van Delden C,, Tümmler B,, Martínez JL,, Rojo F . 2004. Structure of Pseudomonas aeruginosa populations analyzed by single nucleotide polymorphism and pulsed-field gel electrophoresis genotyping. J Bacteriol 186 : 4228 4237.[CrossRef][PubMed]
20. Rahme LG,, Ausubel FM,, Cao H,, Drenkard E,, Goumnerov BC,, Lau GW,, Mahajan-Miklos S,, Plotnikova J,, Tan MW,, Tsongalis J,, Walendziewicz CL,, Tompkins RG . 2000. Plants and animals share functionally common bacterial virulence factors. Proc Natl Acad Sci U S A 97 : 8815 8821.[CrossRef][PubMed]
21. Mahajan-Miklos S,, Rahme LG,, Ausubel FM . 2000. Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts. Mol Microbiol 37 : 981 988.[CrossRef][PubMed]
22. Rahme LG,, Stevens EJ,, Wolfort SF,, Shao J,, Tompkins RG,, Ausubel FM . 1995. Common virulence factors for bacterial pathogenicity in plants and animals. Science 268 : 1899 1902.[CrossRef][PubMed]
23. Wolfgang MC,, Kulasekara BR,, Liang X,, Boyd D,, Wu K,, Yang Q,, Miyada CG,, Lory S . 2003. Conservation of genome content and virulence determinants among clinical and environmental isolates of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 100 : 8484 8489.[CrossRef][PubMed]
24. Libisch B,, Gacs M,, Csiszár K,, Muzslay M,, Rókusz L,, Füzi M . 2004. Isolation of an integron-borne bla VIM-4 type metallo-β-lactamase gene from a carbapenem-resistant Pseudomonas aeruginosa clinical isolate in Hungary. Antimicrob Agents Chemother 48 : 3576 3578.[CrossRef][PubMed]
25. Lee K,, Lim JB,, Yum JH,, Yong D,, Chong Y,, Kim JM,, Livermore DM . 2002. bla VIM-2 cassette-containing novel integrons in metallo-β-lactamase-producing Pseudomonas aeruginosa and Pseudomonas putida isolates disseminated in a Korean hospital. Antimicrob Agents Chemother 46 : 1053 1058.[CrossRef][PubMed]
26. Yizhak K,, Tuller T,, Papp B,, Ruppin E . 2011. Metabolic modeling of endosymbiont genome reduction on a temporal scale. Mol Syst Biol 7 : 479.[CrossRef][PubMed]
27. Pérez-Brocal V,, Gil R,, Ramos S,, Lamelas A,, Postigo M,, Michelena JM,, Silva FJ,, Moya A,, Latorre A . 2006. A small microbial genome: the end of a long symbiotic relationship? Science 314 : 312 313.[CrossRef][PubMed]
28. Gil R,, Latorre A,, Moya A . 2004. Bacterial endosymbionts of insects: insights from comparative genomics. Environ Microbiol 6 : 1109 1122.[CrossRef][PubMed]
29. Tamas I,, Klasson L,, Canbäck B,, Näslund AK,, Eriksson AS,, Wernegreen JJ,, Sandström JP,, Moran NA,, Andersson SG . 2002. 50 million years of genomic stasis in endosymbiotic bacteria. Science 296 : 2376 2379.[CrossRef][PubMed]
30. Brites D,, Gagneux S . 2015. Co-evolution of Mycobacterium tuberculosis and Homo sapiens. Immunol Rev 264 : 6 24.[CrossRef][PubMed]
31. Gagneux S . 2012. Host-pathogen coevolution in human tuberculosis. Philos Trans R Soc Lond B Biol Sci 367 : 850 859.[CrossRef][PubMed]
32. Chouikha I,, Hinnebusch BJ . 2012. Yersinia—flea interactions and the evolution of the arthropod-borne transmission route of plague. Curr Opin Microbiol 15 : 239 246.[CrossRef][PubMed]
33. Zhou D,, Yang R . 2009. Molecular Darwinian evolution of virulence in Yersinia pestis. Infect Immun 77 : 2242 2250.[CrossRef][PubMed]
34. Lesic B,, Carniel E . 2005. Horizontal transfer of the high-pathogenicity island of Yersinia pseudotuberculosis. J Bacteriol 187 : 3352 3358.[CrossRef][PubMed]
35. Zhou D,, Han Y,, Song Y,, Tong Z,, Wang J,, Guo Z,, Pei D,, Pang X,, Zhai J,, Li M,, Cui B,, Qi Z,, Jin L,, Dai R,, Du Z,, Bao J,, Zhang X,, Yu J,, Wang J,, Huang P,, Yang R . 2004. DNA microarray analysis of genome dynamics in Yersinia pestis: insights into bacterial genome microevolution and niche adaptation. J Bacteriol 186 : 5138 5146.[CrossRef][PubMed]
36. Achtman M,, Morelli G,, Zhu P,, Wirth T,, Diehl I,, Kusecek B,, Vogler AJ,, Wagner DM,, Allender CJ,, Easterday WR,, Chenal-Francisque V,, Worsham P,, Thomson NR,, Parkhill J,, Lindler LE,, Carniel E,, Keim P . 2004. Microevolution and history of the plague bacillus, Yersinia pestis. Proc Natl Acad Sci U S A 101 : 17837 17842.[CrossRef][PubMed]
37. Wren BW . 2003. The yersiniae—a model genus to study the rapid evolution of bacterial pathogens. Nat Rev Microbiol 1 : 55 64.[CrossRef][PubMed]
38. Achtman M,, Zurth K,, Morelli G,, Torrea G,, Guiyoule A,, Carniel E . 1999. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proc Natl Acad Sci U S A 96 : 14043 14048.[CrossRef][PubMed]
39. Le Gall T,, Clermont O,, Gouriou S,, Picard B,, Nassif X,, Denamur E,, Tenaillon O . 2007. Extraintestinal virulence is a coincidental by-product of commensalism in B2 phylogenetic group Escherichia coli strains. Mol Biol Evol 24 : 2373 2384.[CrossRef][PubMed]
40. Smati M,, Clermont O,, Bleibtreu A,, Fourreau F,, David A,, Daubié AS,, Hignard C,, Loison O,, Picard B,, Denamur E . 2015. Quantitative analysis of commensal Escherichia coli populations reveals host-specific enterotypes at the intra-species level. MicrobiologyOpen 4 : 604 615.[CrossRef][PubMed]
41. Zhang Y,, Lin K . 2012. A phylogenomic analysis of Escherichia coli/ Shigella group: implications of genomic features associated with pathogenicity and ecological adaptation. BMC Evol Biol 12 : 174.[CrossRef][PubMed]
42. Alteri CJ,, Mobley HL . 2012. Escherichia coli physiology and metabolism dictates adaptation to diverse host microenvironments. Curr Opin Microbiol 15 : 3 9.[CrossRef][PubMed]
43. Carlos C,, Pires MM,, Stoppe NC,, Hachich EM,, Sato MI,, Gomes TA,, Amaral LA,, Ottoboni LM . 2010. Escherichia coli phylogenetic group determination and its application in the identification of the major animal source of fecal contamination. BMC Microbiol 10 : 161.[CrossRef][PubMed]
44. Luo C,, Walk ST,, Gordon DM,, Feldgarden M,, Tiedje JM,, Konstantinidis KT . 2011. Genome sequencing of environmental Escherichia coli expands understanding of the ecology and speciation of the model bacterial species. Proc Natl Acad Sci U S A 108 : 7200 7205.[CrossRef][PubMed]
45. Tenaillon O,, Skurnik D,, Picard B,, Denamur E . 2010. The population genetics of commensal Escherichia coli. Nat Rev Microbiol 8 : 207 217.[CrossRef][PubMed]
46. Milkman R . 1997. Recombination and population structure in Escherichia coli. Genetics 146 : 745 750.[PubMed]
47. Wirth T,, Falush D,, Lan R,, Colles F,, Mensa P,, Wieler LH,, Karch H,, Reeves PR,, Maiden MC,, Ochman H,, Achtman M . 2006. Sex and virulence in Escherichia coli: an evolutionary perspective. Mol Microbiol 60 : 1136 1151.[CrossRef][PubMed]
48. Heesemann J . 2004. Darwin’s principle of divergence revisited: small steps and quantum leaps set the path of microbial evolution. Int J Med Microbiol 294 : 65 66.[CrossRef][PubMed]
49. Ghosh AR . 2013. Appraisal of microbial evolution to commensalism and pathogenicity in humans. Clin Med Insights Gastroenterol 6 : 1 12.[CrossRef][PubMed]
50. Levin BR,, Bull JJ . 1994. Short-sighted evolution and the virulence of pathogenic microorganisms. Trends Microbiol 2 : 76 81.[CrossRef][PubMed]
51. Sokurenko EV,, Gomulkiewicz R,, Dykhuizen DE . 2006. Source-sink dynamics of virulence evolution. Nat Rev Microbiol 4 : 548 555.[CrossRef][PubMed]
52. Martínez-Solano L,, Macia MD,, Fajardo A,, Oliver A,, Martinez JL . 2008. Chronic Pseudomonas aeruginosa infection in chronic obstructive pulmonary disease. Clin Infect Dis 47 : 1526 1533.[CrossRef][PubMed]
53. Oliver A,, Cantón R,, Campo P,, Baquero F,, Blázquez J . 2000. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288 : 1251 1253.[CrossRef][PubMed]
54. van Mansfeld R,, de Vrankrijker A,, Brimicombe R,, Heijerman H,, Teding van Berkhout F,, Spitoni C,, Grave S,, van der Ent C,, Wolfs T,, Willems R,, Bonten M . 2016. The effect of strict segregation on Pseudomonas aeruginosa in cystic fibrosis patients. PLoS One 11 : e0157189.[CrossRef][PubMed]
55. Wiehlmann L,, Cramer N,, Tümmler B . 2015. Habitat-associated skew of clone abundance in the Pseudomonas aeruginosa population. Environ Microbiol Rep 7 : 955 960.[CrossRef][PubMed]
56. Oliver A,, Mulet X,, López-Causapé C,, Juan C . 2015. The increasing threat of Pseudomonas aeruginosa high-risk clones. Drug Resist Updat 21–22 : 41 59.[CrossRef][PubMed]
57. de Vrankrijker AM,, Brimicombe RW,, Wolfs TF,, Heijerman HG,, van Mansfeld R,, van Berkhout FT,, Willems RJ,, Bonten MJ,, van der Ent CK . 2011. Clinical impact of a highly prevalent Pseudomonas aeruginosa clone in Dutch cystic fibrosis patients. Clin Microbiol Infect 17 : 382 385.[CrossRef][PubMed]
58. van Mansfeld R,, Willems R,, Brimicombe R,, Heijerman H,, van Berkhout FT,, Wolfs T,, van der Ent C,, Bonten M . 2009. Pseudomonas aeruginosa genotype prevalence in Dutch cystic fibrosis patients and age dependency of colonization by various P. aeruginosa sequence types. J Clin Microbiol 47 : 4096 4101.[CrossRef][PubMed]
59. San Millan A,, Toll-Riera M,, Qi Q,, MacLean RC . 2015. Interactions between horizontally acquired genes create a fitness cost in Pseudomonas aeruginosa. Nat Commun 6 : 6845.[CrossRef][PubMed]
60. Andersson DI,, Hughes D . 2010. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol 8 : 260 271.[CrossRef][PubMed]
61. Forsberg KJ,, Patel S,, Gibson MK,, Lauber CL,, Knight R,, Fierer N,, Dantas G . 2014. Bacterial phylogeny structures soil resistomes across habitats. Nature 509 : 612 616.[CrossRef][PubMed]
62. Benveniste R,, Davies J . 1973. Aminoglycoside antibiotic-inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic-resistant bacteria. Proc Natl Acad Sci U S A 70 : 2276 2280.[CrossRef][PubMed]
63. Poirel L,, Rodriguez-Martinez JM,, Mammeri H,, Liard A,, Nordmann P . 2005. Origin of plasmid-mediated quinolone resistance determinant QnrA. Antimicrob Agents Chemother 49 : 3523 3525.[CrossRef][PubMed]
64. Humeniuk C,, Arlet G,, Gautier V,, Grimont P,, Labia R,, Philippon A . 2002. β-Lactamases of Kluyvera ascorbata, probable progenitors of some plasmid-encoded CTX-M types. Antimicrob Agents Chemother 46 : 3045 3049.[CrossRef][PubMed]
65. Yoon EJ,, Goussard S,, Touchon M,, Krizova L,, Cerqueira G,, Murphy C,, Lambert T,, Grillot-Courvalin C,, Nemec A,, Courvalin P . 2014. Origin in Acinetobacter guillouiae and dissemination of the aminoglycoside-modifying enzyme Aph(3′)-VI. mBio 5 : e01972-e14.[CrossRef][PubMed]
66. Wright GD . 2010. The antibiotic resistome. Expert Opin Drug Discov 5 : 779 788.[CrossRef][PubMed]
67. D’Costa VM,, McGrann KM,, Hughes DW,, Wright GD . 2006. Sampling the antibiotic resistome. Science 311 : 374 377.[CrossRef][PubMed]
68. Laskaris P,, Tolba S,, Calvo-Bado L,, Wellington EM . 2010. Coevolution of antibiotic production and counter-resistance in soil bacteria. Environ Microbiol 12 : 783 796.[CrossRef][PubMed]
69. Thanassi DG,, Cheng LW,, Nikaido H . 1997. Active efflux of bile salts by Escherichia coli. J Bacteriol 179 : 2512 2518.[CrossRef][PubMed]
70. Ma D,, Cook DN,, Alberti M,, Pon NG,, Nikaido H,, Hearst JE . 1995. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol 16 : 45 55.[CrossRef][PubMed]
71. Jacoby GA . 2009. AmpC β-lactamases. Clin Microbiol Rev 22 : 161 182.[CrossRef][PubMed]
72. Morosini MI,, Ayala JA,, Baquero F,, Martínez JL,, Blázquez J . 2000. Biological cost of AmpC production for Salmonella enterica serotype Typhimurium. Antimicrob Agents Chemother 44 : 3137 3143.[CrossRef][PubMed]
73. Wiedemann B,, Pfeifle D,, Wiegand I,, Janas E . 1998. β-Lactamase induction and cell wall recycling in gram-negative bacteria. Drug Resist Updat 1 : 223 226.[CrossRef]
74. Henderson TA,, Young KD,, Denome SA,, Elf PK . 1997. AmpC and AmpH, proteins related to the class C β-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli. J Bacteriol 179 : 6112 6121.[CrossRef][PubMed]
75. Macinga DR,, Rather PN . 1999. The chromosomal 2′- N-acetyltransferase of Providencia stuartii: physiological functions and genetic regulation. Front Biosci 4 : D132 D140.[CrossRef][PubMed]
76. Piddock LJ . 2006. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev 19 : 382 402.[CrossRef][PubMed]
77. Vila J,, Martínez JL . 2008. Clinical impact of the over-expression of efflux pump in nonfermentative Gram-negative bacilli, development of efflux pump inhibitors. Curr Drug Targets 9 : 797 807.[CrossRef][PubMed]
78. Li XZ,, Plésiat P,, Nikaido H . 2015. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev 28 : 337 418.[CrossRef][PubMed]
79. Hernando-Amado S,, Blanco P,, Alcalde-Rico M,, Corona F,, Reales-Calderón JA,, Sánchez MB,, Martínez JL . 2016. Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials. Drug Resist Updat 28 : 13 27.[CrossRef][PubMed]
80. Piddock LJ . 2006. Multidrug-resistance efflux pumps—not just for resistance. Nat Rev Microbiol 4 : 629 636.[CrossRef][PubMed]
81. Alvarez-Ortega C,, Olivares J,, Martínez JL . 2013. RND multidrug efflux pumps: what are they good for? Front Microbiol 4 : 7.[CrossRef][PubMed]
82. Martinez JL,, Sánchez MB,, Martínez-Solano L,, Hernandez A,, Garmendia L,, Fajardo A,, Alvarez-Ortega C . 2009. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol Rev 33 : 430 449.[CrossRef][PubMed]
83. Martínez JL,, Coque TM,, Baquero F . 2015. Prioritizing risks of antibiotic resistance genes in all metagenomes. Nat Rev Microbiol 13 : 396.[CrossRef][PubMed]
84. Martínez JL,, Coque TM,, Baquero F . 2015. What is a resistance gene? Ranking risk in resistomes. Nat Rev Microbiol 13 : 116 123.[CrossRef][PubMed]
85. Levin BR,, Antia R . 2001. Why we don’t get sick: the within-host population dynamics of bacterial infections. Science 292 : 1112 1115.[CrossRef]
86. Eisenreich W,, Dandekar T,, Heesemann J,, Goebel W . 2010. Carbon metabolism of intracellular bacterial pathogens and possible links to virulence. Nat Rev Microbiol 8 : 401 412.[CrossRef][PubMed]
87. Martínez JL,, Baquero F . 2002. Interactions among strategies associated with bacterial infection: pathogenicity, epidemicity, and antibiotic resistance. Clin Microbiol Rev 15 : 647 679.[CrossRef][PubMed]
88. Martínez JL,, Delgado-Iribarren A,, Baquero F . 1990. Mechanisms of iron acquisition and bacterial virulence. FEMS Microbiol Rev 6 : 45 56.[CrossRef][PubMed]
89. de Lorenzo V,, Martinez JL . 1988. Aerobactin production as a virulence factor: a reevaluation. Eur J Clin Microbiol Infect Dis 7 : 621 629.[CrossRef][PubMed]
90. Trueba G,, Dunthorn M . 2012. Many neglected tropical diseases may have originated in the Paleolithic or before: new insights from genetics. PLoS Negl Trop Dis 6 : e1393.[CrossRef][PubMed]
91. Chouikha I,, Germon P,, Brée A,, Gilot P,, Moulin-Schouleur M,, Schouler C . 2006. A selC-associated genomic island of the extraintestinal avian pathogenic Escherichia coli strain BEN2908 is involved in carbohydrate uptake and virulence. J Bacteriol 188 : 977 987.[CrossRef][PubMed]
92. Luck SN,, Turner SA,, Rajakumar K,, Sakellaris H,, Adler B . 2001. Ferric dicitrate transport system (Fec) of Shigella flexneri 2a YSH6000 is encoded on a novel pathogenicity island carrying multiple antibiotic resistance genes. Infect Immun 69 : 6012 6021.[CrossRef][PubMed]
93. Hacker J,, Carniel E . 2001. Ecological fitness, genomic islands and bacterial pathogenicity. A Darwinian view of the evolution of microbes. EMBO Rep 2 : 376 381.[CrossRef][PubMed]
94. Schubert S,, Rakin A,, Karch H,, Carniel E,, Heesemann J . 1998. Prevalence of the “high-pathogenicity island” of Yersinia species among Escherichia coli strains that are pathogenic to humans. Infect Immun 66 : 480 485.[PubMed]
95. Kirn TJ,, Jude BA,, Taylor RK . 2005. A colonization factor links Vibrio cholerae environmental survival and human infection. Nature 438 : 863 866.[CrossRef][PubMed]
96. Miyata S,, Casey M,, Frank DW,, Ausubel FM,, Drenkard E . 2003. Use of the Galleria mellonella caterpillar as a model host to study the role of the type III secretion system in Pseudomonas aeruginosa pathogenesis. Infect Immun 71 : 2404 2413.[CrossRef][PubMed]
97. Mahajan-Miklos S,, Tan MW,, Rahme LG,, Ausubel FM . 1999. Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96 : 47 56.[CrossRef][PubMed]
98. Carilla-Latorre S,, Calvo-Garrido J,, Bloomfield G,, Skelton J,, Kay RR,, Ivens A,, Martinez JL,, Escalante R . 2008. Dictyostelium transcriptional responses to Pseudomonas aeruginosa: common and specific effects from PAO1 and PA14 strains. BMC Microbiol 8 : 109.[CrossRef][PubMed]
99. Cosson P,, Zulianello L,, Join-Lambert O,, Faurisson F,, Gebbie L,, Benghezal M,, Van Delden C,, Curty LK,, Köhler T . 2002. Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system. J Bacteriol 184 : 3027 3033.[CrossRef][PubMed]
100. Hueck CJ . 1998. Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol Mol Biol Rev 62 : 379 433.[PubMed]
101. Gao LY,, Harb OS,, Abu Kwaik Y . 1997. Utilization of similar mechanisms by Legionella pneumophila to parasitize two evolutionarily distant host cells, mammalian macrophages and protozoa. Infect Immun 65 : 4738 4746.[PubMed]
102. Lainhart W,, Stolfa G,, Koudelka GB . 2009. Shiga toxin as a bacterial defense against a eukaryotic predator, Tetrahymena thermophila. J Bacteriol 191 : 5116 5122.[CrossRef][PubMed]
103. Steinberg KM,, Levin BR . 2007. Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shiga toxin-encoding prophage. Proc Biol Sci 274 : 1921 1929.[CrossRef][PubMed]
104. Pushkareva VI,, Ermolaeva SA . 2010. Listeria monocytogenes virulence factor Listeriolysin O favors bacterial growth in co-culture with the ciliate Tetrahymena pyriformis, causes protozoan encystment and promotes bacterial survival inside cysts. BMC Microbiol 10 : 26.[CrossRef][PubMed]
105. Keim PS,, Wagner DM . 2009. Humans and evolutionary and ecological forces shaped the phylogeography of recently emerged diseases. Nat Rev Microbiol 7 : 813 821.[CrossRef][PubMed]
106. Murros-Kontiainen A,, Johansson P,, Niskanen T,, Fredriksson-Ahomaa M,, Korkeala H,, Björkroth J . 2011. Yersinia pekkanenii sp. nov. Int J Syst Evol Microbiol 61 : 2363 2367.[CrossRef][PubMed]
107. Morelli G,, Song Y,, Mazzoni CJ,, Eppinger M,, Roumagnac P,, Wagner DM,, Feldkamp M,, Kusecek B,, Vogler AJ,, Li Y,, Cui Y,, Thomson NR,, Jombart T,, Leblois R,, Lichtner P,, Rahalison L,, Petersen JM,, Balloux F,, Keim P,, Wirth T,, Ravel J,, Yang R,, Carniel E,, Achtman M . 2010. Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat Genet 42 : 1140 1143.[CrossRef][PubMed]
108. Perry RD,, Fetherston JD . 1997. Yersinia pestis—etiologic agent of plague. Clin Microbiol Rev 10 : 35 66.[PubMed]
109. Ramirez MS,, Traglia GM,, Lin DL,, Tran T,, Tolmasky ME . 2014. Plasmid-mediated antibiotic resistance and virulence in Gram-negatives: the Klebsiella pneumoniae paradigm. Microbiol Spectr 2 : PLAS-0016-2013.[CrossRef]
110. Colonna B,, Ranucci L,, Fradiani PA,, Casalino M,, Calconi A,, Nicoletti M . 1992. Organization of aerobactin, hemolysin, and antibacterial resistance genes in lactose-negative Escherichia coli strains of serotype O4 isolated from children with diarrhea. Infect Immun 60 : 5224 5231.[PubMed]
111. Darfeuille-Michaud A,, Jallat C,, Aubel D,, Sirot D,, Rich C,, Sirot J,, Joly B . 1992. R-plasmid-encoded adhesive factor in Klebsiella pneumoniae strains responsible for human nosocomial infections. Infect Immun 60 : 44 55.[PubMed]
112. Delgado-Iribarren A,, Martinez-Suarez J,, Baquero F,, Perez-Diaz JC,, Martinez JL . 1987. Aerobactin-producing multi-resistance plasmids. J Antimicrob Chemother 19 : 552 553.[CrossRef][PubMed]
113. Martínez-Suárez JV,, Martínez JL,, López de Goicoechea MJ,, Pérez-Díaz JC,, Baquero F,, Meseguer M,, Liñares J . 1987. Acquisition of antibiotic resistance plasmids in vivo by extraintestinal Salmonella spp. J Antimicrob Chemother 20 : 452 453.[CrossRef][PubMed]
114. Bentley SD,, Parkhill J . 2015. Genomic perspectives on the evolution and spread of bacterial pathogens. Proc Biol Sci 282 : 20150488.[CrossRef][PubMed]
115. de la Cruz F,, Davies J . 2000. Horizontal gene transfer and the origin of species: lessons from bacteria. Trends Microbiol 8 : 128 133.[CrossRef][PubMed]
116. Olivares J,, Álvarez-Ortega C,, Martínez JL . 2014. Metabolic compensation of fitness costs associated with overexpression of the multidrug efflux pump MexEF-OprN in Pseudomonas aeruginosa. Antimicrob Agents Chemother 58 : 3904 3913.[CrossRef][PubMed]
117. Schulz zur Wiesch P,, Engelstädter J,, Bonhoeffer S . 2010. Compensation of fitness costs and reversibility of antibiotic resistance mutations. Antimicrob Agents Chemother 54 : 2085 2095.[CrossRef][PubMed]
118. Andersson DI . 2006. The biological cost of mutational antibiotic resistance: any practical conclusions? Curr Opin Microbiol 9 : 461 465.[CrossRef][PubMed]
119. Gould SJ,, Lloyd EA . 1999. Individuality and adaptation across levels of selection: how shall we name and generalize the unit of Darwinism? Proc Natl Acad Sci U S A 96 : 11904 11909.[CrossRef][PubMed]
120. Gould SJ,, Vrba S . 1982. Exaptation: a missing term in the science of form. Paleobiology 8 : 4 15.[CrossRef]
121. Olivares J,, Alvarez-Ortega C,, Linares JF,, Rojo F,, Köhler T,, Martínez JL . 2012. Overproduction of the multidrug efflux pump MexEF-OprN does not impair Pseudomonas aeruginosa fitness in competition tests, but produces specific changes in bacterial regulatory networks. Environ Microbiol 14 : 1968 1981.[CrossRef][PubMed]
122. Lamarche MG,, Déziel E . 2011. MexEF-OprN efflux pump exports the Pseudomonas quinolone signal (PQS) precursor HHQ (4-hydroxy-2-heptylquinoline). PLoS One 6 : e24310.[CrossRef][PubMed]
123. Köhler T,, van Delden C,, Curty LK,, Hamzehpour MM,, Pechere JC . 2001. Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa. J Bacteriol 183 : 5213 5222.[CrossRef][PubMed]
124. Evans K,, Passador L,, Srikumar R,, Tsang E,, Nezezon J,, Poole K . 1998. Influence of the MexAB-OprM multidrug efflux system on quorum sensing in Pseudomonas aeruginosa. J Bacteriol 180 : 5443 5447.[PubMed]
125. Martínez JL . 2012. Natural antibiotic resistance and contamination by antibiotic resistance determinants: the two ages in the evolution of resistance to antimicrobials. Front Microbiol 3 : 1.[CrossRef][PubMed]
126. Martinez JL . 2009. The role of natural environments in the evolution of resistance traits in pathogenic bacteria. Proc Biol Sci 276 : 2521 2530.[CrossRef][PubMed]
127. Baquero F,, Alvarez-Ortega C,, Martinez JL . 2009. Ecology and evolution of antibiotic resistance. Environ Microbiol Rep 1 : 469 476.[CrossRef][PubMed]
128. Martínez JL . 2012. Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens. Front Microbiol 2 : 265.[CrossRef][PubMed]
129. Berendonk TU,, Manaia CM,, Merlin C,, Fatta-Kassinos D,, Cytryn E,, Walsh F,, Bürgmann H,, Sørum H,, Norström M,, Pons MN,, Kreuzinger N,, Huovinen P,, Stefani S,, Schwartz T,, Kisand V,, Baquero F,, Martinez JL . 2015. Tackling antibiotic resistance: the environmental framework. Nat Rev Microbiol 13 : 310 317.[CrossRef][PubMed]
130. Baquero F,, Martínez JL,, Cantón R . 2008. Antibiotics and antibiotic resistance in water environments. Curr Opin Biotechnol 19 : 260 265.[CrossRef][PubMed]
131. Cabello FC,, Godfrey HP,, Tomova A,, Ivanova L,, Dölz H,, Millanao A,, Buschmann AH . 2013. Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health. Environ Microbiol 15 : 1917 1942.[CrossRef][PubMed]
132. Chen MY,, Lira F,, Liang HQ,, Wu RT,, Duan JH,, Liao XP,, Martínez JL,, Liu YH,, Sun J . 2016. Multilevel selection of bcrABDR-mediated bacitracin resistance in Enterococcus faecalis from chicken farms. Sci Rep 6 : 34895.[CrossRef][PubMed]
133. Köhler CD,, Dobrindt U . 2011. What defines extraintestinal pathogenic Escherichia coli? Int J Med Microbiol 301 : 642 647.[CrossRef][PubMed]
134. San Millan A,, Toll-Riera M,, Qi Q,, MacLean RC . 2015. Interactions between horizontally acquired genes create a fitness cost in Pseudomonas aeruginosa. Nat Commun 6 : 6845.[CrossRef][PubMed]
135. Baltrus DA . 2013. Exploring the costs of horizontal gene transfer. Trends Ecol Evol 28 : 489 495.[CrossRef][PubMed]
136. Starikova I,, Harms K,, Haugen P,, Lunde TT,, Primicerio R,, Samuelsen Ø,, Nielsen KM,, Johnsen PJ . 2012. A trade-off between the fitness cost of functional integrases and long-term stability of integrons. PLoS Pathog 8 : e1003043.[CrossRef][PubMed]
137. Park C,, Zhang J . 2012. High expression hampers horizontal gene transfer. Genome Biol Evol 4 : 523 532.[CrossRef][PubMed]
138. Johnsen PJ,, Levin BR . 2010. Adjusting to alien genes. Mol Microbiol 75 : 1061 1063.[CrossRef][PubMed]
139. Knöppel A,, Lind PA,, Lustig U,, Näsvall J,, Andersson DI . 2014. Minor fitness costs in an experimental model of horizontal gene transfer in bacteria. Mol Biol Evol 31 : 1220 1227.[CrossRef][PubMed]
140. Schaufler K,, Semmler T,, Pickard DJ,, de Toro M,, de la Cruz F,, Wieler LH,, Ewers C,, Guenther S . 2016. Carriage of extended-spectrum beta-lactamase-plasmids does not reduce fitness but enhances virulence in some strains of pandemic E. coli lineages. Front Microbiol 7 : 336.[CrossRef][PubMed]
141. Sánchez MB,, Martínez JL . 2012. Differential epigenetic compatibility of qnr antibiotic resistance determinants with the chromosome of Escherichia coli. PLoS One 7 : e35149.[CrossRef][PubMed]
142. Björkman J,, Nagaev I,, Berg OG,, Hughes D,, Andersson DI . 2000. Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance. Science 287 : 1479 1482.[CrossRef][PubMed]
143. Handel A,, Regoes RR,, Antia R . 2006. The role of compensatory mutations in the emergence of drug resistance. PLoS Comput Biol 2 : e137.[CrossRef][PubMed]
144. Maisnier-Patin S,, Berg OG,, Liljas L,, Andersson DI . 2002. Compensatory adaptation to the deleterious effect of antibiotic resistance in Salmonella typhimurium. Mol Microbiol 46 : 355 366.[CrossRef][PubMed]
145. Böttger EC,, Springer B,, Pletschette M,, Sander P . 1998. Fitness of antibiotic-resistant microorganisms and compensatory mutations. Nat Med 4 : 1343 1344.[CrossRef][PubMed]
146. Hernando-Amado S,, Sanz-García F,, Blanco P,, Martínez JL . 2017. Fitness costs associated with the acquisition of antibiotic resistance. Essays Biochem 61 : 37 48.[CrossRef][PubMed]
147. Martínez JL,, Baquero F . 2014. Emergence and spread of antibiotic resistance: setting a parameter space. Ups J Med Sci 119 : 68 77.[CrossRef][PubMed]
148. Fitzpatrick D,, Walsh F . 2016. Antibiotic resistance genes across a wide variety of metagenomes. FEMS Microbiol Ecol 92 : 92.[CrossRef]
149. Hu Y,, Yang X,, Qin J,, Lu N,, Cheng G,, Wu N,, Pan Y,, Li J,, Zhu L,, Wang X,, Meng Z,, Zhao F,, Liu D,, Ma J,, Qin N,, Xiang C,, Xiao Y,, Li L,, Yang H,, Wang J,, Yang R,, Gao GF,, Wang J,, Zhu B . 2013. Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nat Commun 4 : 2151.[CrossRef][PubMed]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error