6 : Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens

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A pathogenic organism can be seen as an ‘‘emerging’’ pathogen in several ways. It may be a newly discovered organism, an organism that has acquired new virulence factors or antibiotic resistance, or a well-known pathogen for which newly discovered subpopulations of the parent strain are able to produce disease. small-colony variants (SCVs) fall into the last category. In SCVs, reversal of the SCV phenotype by adding compounds that can be utilized to repair the defect in electron transport simultaneously or by complementing the genetic defect in trans enhances alpha-toxin production. Well-characterized hemin biosynthetic mutants demonstrate an SCV phenotype, including decreased coagulase activity, aminoglycoside resistance, decreased pigmentation, slow growth, and reduced hemolytic activity. Anaerobic growth downregulates menaquinone biosynthesis in and electron transport. Taken together, these observations show that alpha-toxin production is dependent upon electron transport. Carotenoid pigments that give SCV colonies their characteristic yellow color require ATP for their biosynthesis. Aminoglycoside uptake by is an energy-dependent process that requires ATP and an electrochemical gradient, which is produced via the electron transport system.

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6
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Figure 1

Relationship between electron transport and SCV phenotype in . Clinical SCV isolates are frequently found to grow more rapidly when supplemented with thiamine, menadione, or hemin. Each of these substances is a component of the quinone or the cytochromes that constitute part of the electron transport chain. Intact electron transport provides ATP through the biosynthetic enzyme, the FF ATPase; creates an electrochemical gradient across the cell membrane; and is involved in carotenoid biosynthesis. Interruption of electron transport because of the loss of one of the components in the chain or due to anaerobic growth causes multiple phenotypic changes. The organisms grow slowly, have reduced pigmentation, and are more resistant to antibiotics. Cell wall-active antibiotics are less effective because of the low rate of bacterial growth. The smaller negative membrane charge in bacteria deficient in electron transport results in decreased binding of positively charged antibiotics to the membrane. FADH, reduced flavin adenine dinucleotide.

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6
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Figure 2

Hypothetical model for regulation of virulence factors in . This is a schematic representation of several signaling factors that have been proposed to regulate staphylococcal virulence factor production. The sensor portions of the two-component regulators (SaeS, ResE, and AgrC) are shown as transmembrane proteins. The cognate response regulators (SaeR, ResD, and AgrA) are thought to be activated (phosphorylated) by the sensor proteins when stimulated. Solid arrows represent positive actions, whereas dashed arrows indicate negative signaling. The locus (accessory gene regulator) was the first reported global regulator of staphylococcal toxins. The operon includes a protein that is processed and released from the bacteria as an autoregulatory cyclic thiolactone peptide. RNAIII is the message from , and it has a dual role. When translated, δ-hemolysin is produced. However, when nontranscribed, RNAIII is an effector molecule that is involved in the regulation of a number of genes involved in the production of virulence factors. Sar (staphylococcal accessory regulator) was subsequently identified and found to positively regulate Agr. SaeRS ( extracellular protein regulator) has recently been identified, and both its positive and negative actions are thought to act after RNAIII. Other protein regulators include Rot, Rlp, Sar, SarR, and SarH1. σ is a stress sigma factor that has negative regulatory effects on Sar. The activity of σ increases as ATP levels drop, thereby giving it a connection to electron transport. ResDE homologues have been identified in , but their precise role in regulating exoprotein production is still undefined; therefore, a question mark is placed by this arrow.

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6
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Table 1

Regulation of staphylococcal toxin production

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6
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Table 2

SCV phenotype and exoprotein regulation in

Citation: Proctor R, Bates D, McNamara P. 2001. Electron Transport-Deficient Staphylococcus aureus Small-Colony Variants as Emerging Pathogens, p 95-110. In Scheld W, Craig W, Hughes J (ed), Emerging Infections 5. ASM Press, Washington, DC. doi: 10.1128/9781555816988.ch6

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