Persistence of<i>Streptococcus pyogenes</i>in Stationary-Phase Cultures

Wood, Daniel N.; Chaussee, Michelle A.; Chaussee, Michael S.; Buttaro, Bettina A.

doi:10.1128/jb.187.10.3319-3328.2005

Cited by 36 publications

(54 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many other human pathogens, including Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, are similarly able to enter a drug-refractory state (14)(15)(16)(17). Work in E. coli mutants has suggested that, in a bacterial population, persisters exist before antibiotic exposure (18).…”

mentioning

confidence: 99%

Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals

Grant

Kaufmann²,

Chand³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

230

211

View full text Add to dashboard Cite

During Mycobacterium tuberculosis infection, a population of bacteria likely becomes refractory to antibiotic killing in the absence of genotypic resistance, making treatment challenging. We describe an in vitro model capable of yielding a phenotypically antibiotic-tolerant subpopulation of cells, often called persisters, within populations of Mycobacterium smegmatis and M. tuberculosis . We find that persisters are distinct from the larger antibiotic-susceptible population, as a small drop in dissolved oxygen (DO) saturation (20%) allows for their survival in the face of bactericidal antibiotics. In contrast, if high levels of DO are maintained, all cells succumb, sterilizing the culture. With increasing evidence that bactericidal antibiotics induce cell death through the production of reactive oxygen species (ROS), we hypothesized that the drop in DO decreases the concentration of ROS, thereby facilitating persister survival, and maintenance of high DO yields sufficient ROS to kill persisters. Consistent with this hypothesis, the hydroxyl-radical scavenger thiourea, when added to M. smegmatis cultures maintained at high DO levels, rescues the persister population. Conversely, the antibiotic clofazimine, which increases ROS via an NADH-dependent redox cycling pathway, successfully eradicates the persister population. Recent work suggests that environmentally induced antibiotic tolerance of bulk populations may result from enhanced antioxidant capabilities. We now show that the small persister subpopulation within a larger antibiotic-susceptible population also shows differential susceptibility to antibiotic-induced hydroxyl radicals. Furthermore, we show that stimulating ROS production can eradicate persisters, thus providing a potential strategy to managing persistent infections.

show abstract

mentioning

confidence: 99%

Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals

Grant

Kaufmann²,

Chand³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

230

211

View full text Add to dashboard Cite

show abstract

“…Only one alternate sigma factor, SigX, has been described for S. pyogenes (51). SigX is not important for exponential growth, regulation of most known virulence factors, stress tolerance, biofilm formation, or stationary-phase survival (51,83,84). SigX directly influences transcription of putative competence genes and the putative cell wall cross-linking enzyme gene femB (84).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…We have found that S. pyogenes can survive up to 1.5 years in complex medium (Todd-Hewitt [TH] broth) (83). Long-term survival is dependent on the maintenance of culture pH above ϳ5.6, and any decrease of the pH below this threshold significantly truncates survival (83). Individual strains isolated from long-term stationary-phase cultures accumulate mutations that lead to altered colony morphologies and unique exponential-phase proteomes (40,83).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Generation of Metabolically Diverse Strains ofStreptococcus pyogenesduring Survival in Stationary Phase

et al. 2009

Self Cite

View full text Add to dashboard Cite

Streptococcus pyogenes, in addition to causing fulminant disease, can be carried asymptomatically and may survive in the host without causing disease. Long-term stationary-phase cultures were used to characterize the metabolism of cultures surviving after glucose depletion. Survival of stationary-phase cultures in glucosedepleted rich medium was truncated by switching the cells to phosphate-buffered saline or by the addition of antibiotics, suggesting that survival depended on the presence of nutrients and metabolic activity. The metabolites of the pyruvate-to-acetate (PA) pathway (acetate and formate) and amino acid catabolic pathways (ammonia) accumulated throughout long-term stationary phase (12 weeks). Acid and ammonia production was balanced so that the culture pH was maintained above pH 5.6. Strains isolated from long-term stationaryphase cultures accumulated mutations that resulted in unique exponential-phase metabolisms, with some strains expressing the PA pathway, some strains producing ammonia, and some strains expressing both in the presence of glucose. Strains expressing high levels of PA pathway activity during exponential growth were unable to survive when regrown in pure culture due to the production of excess acid. These data suggest that S. pyogenes diversifies during survival in stationary phase into distinct strains with different metabolisms and that complementary metabolism is required to control the pH in stationary-phase cultures. One of three survivor strains isolated from tonsillar discard material from patients expressed high levels of the PA pathway during exponential growth. Sequencing of multiple group A streptococcus regulators revealed two different mutations in two different strains, suggesting that random mutation occurs during survival.The human pathogen Streptococcus pyogenes (group A streptococcus [GAS]) is the causative agent of mild infections (e.g., impetigo and pharyngitis), severe disease (e.g., toxic shock syndrome and necrotizing fasciitis), and secondary sequelae (e.g., rheumatic fever and glomerulonephritis) (reviewed in references 17 and 32). Asymptomatic carriage and antibiotic treatment failure suggest that S. pyogenes may be able to persist in the host after the initial infection (5, 7). S. pyogenes asymptomatic carriage rates of 2.5% to 32% have been observed with large cohorts of school-age children worldwide (2,16,23,46,56,57,63,64). Carriage in adults is less frequent (1.3% to 4.9%) but has been observed with adult health care workers and military recruits (9, 34). Although not all cases of recurrent tonsillitis are clonal, carriage of S. pyogenes has been implicated as one of the causes of recurrent tonsillitis (5,7,8,46,52,53,56,59). In addition to recurrent tonsillitis, carriers have been associated with outbreaks of invasive disease (9, 15).Since the carried bacteria do not cause fulminant infection during carriage, it is likely that they survive in an altered growth state. Survival of bacteria has been characterized for both gram-negative and gram-positiv...

show abstract

“…Streptococci have been shown to internalize in tonsillar epithelial cells, live inside the cells for up to a year, then externalize and recolonize [4]. When they are inside the cells, their presence is not detectable either by culture or serology.…”

Section: Psoriasis-discussion Of Microbial Pathogenesis Of the Diseasementioning

confidence: 99%

Bioethics and Psoriasis

Allen¹,

Allawh²,

Ogrich³

et al. 2017

J Clin Res Bioeth

View full text Add to dashboard Cite

We have presented the clinical, epidemiological, microbiological, pathological, immunopathological, serological, and therapeutic studies showing how the streptococcus may be strongly linked to psoriasis. With this as background, we have presented three ethical arguments that are cogent for psoriasis. First, this microbial "pathogen" theory is both ignored and overlooked even with the abundance of evidence supporting it. That being the case, current treatments, consequently, are aimed not at the onset of the disease, but much later in the pathogenic cascade. Last, the continued use of "biologics" or costly immunosuppressives, which are not curative, presents bioethical challenges. We consider psoriasis a sequela of streptococcal infection similar to rheumatic fever, where treatment, at the earliest stages of the disease, has resulted in its disappearance.

show abstract

Persistence ofStreptococcus pyogenesin Stationary-Phase Cultures

Cited by 36 publications

References 56 publications

Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals

Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals

Generation of Metabolically Diverse Strains ofStreptococcus pyogenesduring Survival in Stationary Phase

Bioethics and Psoriasis

Contact Info

Product

Resources

About