Dataset Information

Immune response modulation by Pseudomonas aeruginosa persister cells.

ABSTRACT: Bacterial persister cells - a metabolically dormant subpopulation tolerant to antimicrobials - contribute to chronic infections and are thought to evade host immunity. In this work, we studied the ability of Pseudomonas aeruginosa persister cells to withstand host innate immunity. We found that persister cells resist MAC-mediated killing by the complement system despite being bound by complement protein C3b at levels similar to regular vegetative cells, in part due to reduced bound C5b - and are engulfed at a lower rate (10-100 fold), even following opsonization. Once engulfed, persister cells resist killing and, contrary to regular vegetative cells which induce a M1 favored (CD80+/CD86+/CD206-, high levels of CXCL-8, IL-6, and TNF-α) macrophage polarization, they initially induce a M2 favored macrophage polarization (CD80+/CD86+/CD206+, high levels of IL-10, and intermediate levels of CXCL-8, IL-6, and TNF-α), which is skewed towards M1 favored polarization (high levels of CXCL-8 and IL-6, lower levels of IL-10) by 24 hours of infection, once persister cells awaken. Overall, our findings further establish the ability of persister cells to evade the innate host response and to contribute chronic infections.

SUBMITTER: Hastings CJ

PROVIDER: S-EPMC9881899 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immune response modulation by <i>Pseudomonas aeruginosa</i> persister cells.

Hastings Cody James CJ Himmler Grace Elizabeth GE Patel Arpeet A Marques Cláudia Nogueira Hora CNH

bioRxiv : the preprint server for biology 20230108

Bacterial persister cells - a metabolically dormant subpopulation tolerant to antimicrobials - contribute to chronic infections and are thought to evade host immunity. In this work, we studied the ability of <i>Pseudomonas aeruginosa</i> persister cells to withstand host innate immunity. We found that persister cells resist MAC-mediated killing by the complement system despite being bound by complement protein C3b at levels similar to regular vegetative cells, in part due to reduced bound C5b - ...[more]

PMID: 36711557

Similar Datasets

Project description:Biofilms are commonly recalcitrant to antibiotics, through incompletely elucidated mechanisms such as tolerance and persistence. We aimed at investigating how a Pseudomonas aeruginosa biofilm escapes ciprofloxacin treatment. P. aeruginosa PA14 in vitro mature biofilms were challenged with supra-MIC ciprofloxacin concentrations. Cell viability was quantified by fluorescein diacetate assay. Population dynamics were determined by counts of surviving culturable cells. Biofilms were analyzed using confocal laser scanning microscopy (CLSM), and the expression of genes involved in stringent response, toxin-antitoxin HigB/HigA, and type 3 secretion system (T3SS) was quantified by RT-qPCR in untreated and treated biofilms. Ciprofloxacin exposure resulted in an initial reduction of bacterial counts following a biphasic time-kill curve. After 24 h of treatment, the overall cell activity and the density of culturable cells significantly decreased as compared to untreated biofilm. No resistant mutant was isolated among the <1% surviving cells. Phenotypic adaptation toward persistence appeared to start after only 1 h of antibiotic exposure, by an overexpression of the genes involved in stringent response and in the toxin-antitoxin system, whereas the expression of genes encoding for the T3SS remained unchanged. After 4 h of ciprofloxacin exposure, stringent response genes returned to their basal level of expression. After a prolonged ciprofloxacin exposure, a deep alteration in the matrix structure that became thinner and lost mushroom-like aggregates was observed, in relation with reduced biovolumes of exopolysaccharides and extracellular DNA. These results support that ciprofloxacin might first induce the bacterial killing of most bacterial cells, but simultaneously activate stringent response mechanisms contributing to the switch of a subpopulation toward a persister phenotype. Once the persister phenotype is expressed, and despite an unexpected alteration of the biofilm matrix, ciprofloxacin fails to eradicate biofilm.

Dataset Information

Immune response modulation by Pseudomonas aeruginosa persister cells.

Publications

Immune response modulation by <i>Pseudomonas aeruginosa</i> persister cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets