Limits...
Persistent Staphylococcus aureus isolates from two independent cases of bacteremia display increased bacterial fitness and novel immune evasion phenotypes.

Richards RL, Haigh RD, Pascoe B, Sheppard SK, Price F, Jenkins D, Rajakumar K, Morrissey JA - Infect. Immun. (2015)

Bottom Line: Several novel traits were associated specifically with both independent sets of persistent S. aureus isolates compared to both the initial isolates and the isolates from resolved infections (resolved isolates).These traits included (i) increased growth under nutrient-poor conditions; (ii) increased tolerance of iron toxicity; (iii) higher expression of cell surface proteins involved in immune evasion and stress responses; and (iv) attenuated virulence in a Galleria mellonella larva infection model that was not associated with small-colony variation or metabolic dormancy such as had been seen previously.Overall, our data indicate a novel role for MprF function during development of S. aureus persistence by increasing bacterial fitness and immune evasion.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Infection, Immunity of Inflammation, University of Leicester, Leicester, United Kingdom.

Show MeSH

Related in: MedlinePlus

Galleria mellonella larva virulence assay. (A) Groups of 10 Galleria larvae were injected with ∼106 CFU of bacteria and fatalities recorded every 24 h over a 96-h period. Data were plotted on Kaplan-Meier survival plots and log-rank tests used to determine significance. Significance is indicated with asterisks. *, P < 0.05; **, P < 0.01; ****, P < 0.0001. (B) Bacterial CFU levels were calculated from individual homogenized larva using selective media. (C) Total RNA was extracted from homogenized larvae, and 16S rRNA was quantified via qRT-PCR. CT values were inverted and multiplied by 1,000 to give manageable relative values for comparisons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4496624&req=5

Figure 7: Galleria mellonella larva virulence assay. (A) Groups of 10 Galleria larvae were injected with ∼106 CFU of bacteria and fatalities recorded every 24 h over a 96-h period. Data were plotted on Kaplan-Meier survival plots and log-rank tests used to determine significance. Significance is indicated with asterisks. *, P < 0.05; **, P < 0.01; ****, P < 0.0001. (B) Bacterial CFU levels were calculated from individual homogenized larva using selective media. (C) Total RNA was extracted from homogenized larvae, and 16S rRNA was quantified via qRT-PCR. CT values were inverted and multiplied by 1,000 to give manageable relative values for comparisons.

Mentions: The general virulence behavior of the initial or persistent EMRSA-15 isolates was compared to that of the control resolved EMRSA-15 bacteremia isolates using a Galleria mellonella larva infection model where larvae mortalities are recorded every 24 h over a 96-h period (Fig. 7A). Persistent isolates associated with both PB1 and PB3 showed significantly lower virulence than the respective initial isolates (PB1-15-1, P < 0.001; PB1-15-2, P < 0.001; PB3-32, P < 0.01). There was also a significant difference between PB3-32-1 and PB3-74 (P < 0.05), with the latter exhibiting an enhanced Galleria killing phenotype equivalent to that seen with the PB3-1 initial isolate.


Persistent Staphylococcus aureus isolates from two independent cases of bacteremia display increased bacterial fitness and novel immune evasion phenotypes.

Richards RL, Haigh RD, Pascoe B, Sheppard SK, Price F, Jenkins D, Rajakumar K, Morrissey JA - Infect. Immun. (2015)

Galleria mellonella larva virulence assay. (A) Groups of 10 Galleria larvae were injected with ∼106 CFU of bacteria and fatalities recorded every 24 h over a 96-h period. Data were plotted on Kaplan-Meier survival plots and log-rank tests used to determine significance. Significance is indicated with asterisks. *, P < 0.05; **, P < 0.01; ****, P < 0.0001. (B) Bacterial CFU levels were calculated from individual homogenized larva using selective media. (C) Total RNA was extracted from homogenized larvae, and 16S rRNA was quantified via qRT-PCR. CT values were inverted and multiplied by 1,000 to give manageable relative values for comparisons.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496624&req=5

Figure 7: Galleria mellonella larva virulence assay. (A) Groups of 10 Galleria larvae were injected with ∼106 CFU of bacteria and fatalities recorded every 24 h over a 96-h period. Data were plotted on Kaplan-Meier survival plots and log-rank tests used to determine significance. Significance is indicated with asterisks. *, P < 0.05; **, P < 0.01; ****, P < 0.0001. (B) Bacterial CFU levels were calculated from individual homogenized larva using selective media. (C) Total RNA was extracted from homogenized larvae, and 16S rRNA was quantified via qRT-PCR. CT values were inverted and multiplied by 1,000 to give manageable relative values for comparisons.
Mentions: The general virulence behavior of the initial or persistent EMRSA-15 isolates was compared to that of the control resolved EMRSA-15 bacteremia isolates using a Galleria mellonella larva infection model where larvae mortalities are recorded every 24 h over a 96-h period (Fig. 7A). Persistent isolates associated with both PB1 and PB3 showed significantly lower virulence than the respective initial isolates (PB1-15-1, P < 0.001; PB1-15-2, P < 0.001; PB3-32, P < 0.01). There was also a significant difference between PB3-32-1 and PB3-74 (P < 0.05), with the latter exhibiting an enhanced Galleria killing phenotype equivalent to that seen with the PB3-1 initial isolate.

Bottom Line: Several novel traits were associated specifically with both independent sets of persistent S. aureus isolates compared to both the initial isolates and the isolates from resolved infections (resolved isolates).These traits included (i) increased growth under nutrient-poor conditions; (ii) increased tolerance of iron toxicity; (iii) higher expression of cell surface proteins involved in immune evasion and stress responses; and (iv) attenuated virulence in a Galleria mellonella larva infection model that was not associated with small-colony variation or metabolic dormancy such as had been seen previously.Overall, our data indicate a novel role for MprF function during development of S. aureus persistence by increasing bacterial fitness and immune evasion.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Infection, Immunity of Inflammation, University of Leicester, Leicester, United Kingdom.

Show MeSH
Related in: MedlinePlus