Subinhibitory Concentrations of Antibiotics Alter the Response of Klebsiella pneumoniae to Components of Innate Host Defense
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PROVIDER: PRJNA831278 | ENA |
REPOSITORIES: ENA
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Project description:Carbapenem-resistant Klebsiella pneumoniae classified as multilocus sequence type 258 (ST258)are a problem in healthcare settings in many countries globally. ST258 isolates are resistant tomultiple classes of antibiotics and can cause life-threatening infections, such as pneumonia andsepsis, in susceptible individuals. Treatment strategies for such infections are limited. Hence,understanding the response of K. pneumoniae to host factors in the presence of antibiotics couldreveal mechanisms employed by the pathogen to evade killing in the susceptible host, as well asinform treatment of infections. Here, we investigated the ability of subinhibitory concentrationsof antibiotics to alter K. pneumoniae capsule polysaccharide (CPS) production and survival innormal human serum. Several antibiotics tested enhanced ST258 survival in normal humanserum. Unexpectedly, subinhibitory concentrations of mupirocin increased survival in 7 of 10clinical isolates tested, and caused up-regulated expression of CPS biosynthesis genes and CPSproduction in a selected ST258 clinical isolate (34446) compared with untreated controls.Additionally, mupirocin treatment caused a reduction in the deposition of the serum complementproteins C3b and C5b-9 on the surface of ST258. Transcriptome analyses with isolate 34446indicated that genes implicated in serum resistance, such as aroE, csrD, pyrB, pyrC and traT,were up-regulated following mupirocin treatment. In conclusion, mupirocin causes changes inthe K. pneumoniae transcriptome that likely contribute to the observed decrease in serumsusceptibility via a multifactorial process. Whether these responses are triggered by othercomponents of host defense or therapeutics that were not tested here merits further investigation.
2022-10-12 | GSE201383 | GEO
Project description:Carbapenem-resistant Klebsiella pneumoniae isolates classified as multilocus sequence type 258 (ST258) are a problem in health care settings in many countries globally. ST258 isolates are resistant to multiple classes of antibiotics and can cause life-threatening infections, such as pneumonia and sepsis, in susceptible individuals. Treatment strategies for such infections are limited. Understanding the response of K. pneumoniae to host factors in the presence of antibiotics could reveal mechanisms employed by the pathogen to evade killing in the susceptible host, as well as inform treatment of infections. Here, we investigated the ability of antibiotics at subinhibitory concentrations to alter K. pneumoniae capsular polysaccharide (CPS) production and survival in normal human serum (NHS). Unexpectedly, pretreatment with some of the antibiotics tested enhanced ST258 survival in NHS. For example, a subinhibitory concentration of mupirocin increased survival for 7 of 10 clinical isolates evaluated and there was increased cell-associated CPS for 3 of these isolates compared with untreated controls. Additionally, mupirocin pretreatment caused concomitant reduction in the deposition of the serum complement protein C5b-9 on the surface of these three isolates. Transcriptome analyses with a selected ST258 isolate (34446) indicated that genes implicated in the stringent response and/or serum resistance were upregulated following mupirocin treatment and/or culture in NHS. In conclusion, mupirocin and/or human serum causes changes in the K. pneumoniae transcriptome that likely contribute to the observed decrease in serum susceptibility via a multifactorial process. Whether these responses can be extended more broadly and thus impact clinical outcome in the human host merits further investigation. IMPORTANCE The extent to which commensal bacteria are altered by exposure to subinhibitory concentrations of antibiotics (outside resistance) remains incompletely determined. To gain a better understanding of this phenomenon, we tested the ability of selected antibiotics (at subinhibitory concentrations) to alter survival of ST258 clinical isolates in normal human serum. We found that exposure of ST258 to antibiotics at low concentrations differentially altered gene expression, capsule production, serum complement deposition, and bacterial survival. The findings were isolate and antibiotic dependent but provide insight into a potential confounding issue associated with ST258 infections.
| S-EPMC9769900 | biostudies-literature
Project description:Expression profiling on a total of 4,391 genes was conducted to identify regulated S. typhimurium genes upon exposure to subinhibitory concentrations of the MEP pathway antibiotic fosmidomycin. These results were subsequently compared to a similar gene expression analysis of subinhibitory exposures of S. typhimurium to the bactericide kanamycin
2016-08-28 | GSE50480 | GEO
Project description:Objectives: The aim of the study was to investigate the Campylobacter jejuni response to subinhibitory concentrations of natural antimicrobial compound pinocembrin
2017-08-31 | GSE72760 | GEO
Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are often caused by strains encoding Panton-Valentine leukocidin (PVL). PVL can cause lysis of polymorphonuclear leukocytes (PMNs) and other myeloid cells in vitro, a function considered widely as the primary means by which PVL might contribute to disease. However, at sublytic concentrations PVL can function as a PMN agonist. To better understand this phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs exposed to PVL had enhanced capacity to produce superoxide in response to N-formyl-methionyl-leucyl-phenylalanine (fMLF), but unlike priming by lipopolysaccharide, this response did not require Toll-like receptor signal transduction. On the other hand, there was subcellular redistribution of NADPH oxidase components in PMNs following exposure of these cells to PVL - a finding consistent with priming. Priming of PMNs with other agonists such as IL-8 or GM-CSF altered the ability PVL to cause formation of pores in the plasma membranes of these cells. Microarray analysis revealed significant changes in the human PMN transcriptome following exposure to PVL, including up-regulation of molecules that regulate the inflammatory response. Consistent with the microarray data, mediators of the inflammatory response were released from PMNs after stimulation with PVL. We conclude that exposure of human PMNs to sublytic concentrations of PVL elicits a proinflammatory response that is regulated in part at the level of gene expression. We propose that PVL-mediated priming of PMNs enhances the host innate immune response. time series of PMN's non treated vs PVL treated vs iPVL treated
2012-09-06 | E-GEOD-33939 | biostudies-arrayexpress
Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are often caused by strains encoding Panton-Valentine leukocidin (PVL). PVL can cause lysis of polymorphonuclear leukocytes (PMNs) and other myeloid cells in vitro, a function considered widely as the primary means by which PVL might contribute to disease. However, at sublytic concentrations PVL can function as a PMN agonist. To better understand this phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs exposed to PVL had enhanced capacity to produce superoxide in response to N-formyl-methionyl-leucyl-phenylalanine (fMLF), but unlike priming by lipopolysaccharide, this response did not require Toll-like receptor signal transduction. On the other hand, there was subcellular redistribution of NADPH oxidase components in PMNs following exposure of these cells to PVL - a finding consistent with priming. Priming of PMNs with other agonists such as IL-8 or GM-CSF altered the ability PVL to cause formation of pores in the plasma membranes of these cells. Microarray analysis revealed significant changes in the human PMN transcriptome following exposure to PVL, including up-regulation of molecules that regulate the inflammatory response. Consistent with the microarray data, mediators of the inflammatory response were released from PMNs after stimulation with PVL. We conclude that exposure of human PMNs to sublytic concentrations of PVL elicits a proinflammatory response that is regulated in part at the level of gene expression. We propose that PVL-mediated priming of PMNs enhances the host innate immune response.
2012-09-06 | GSE33939 | GEO
Project description:Biocides are chemical compounds widely used in hospital settings for a variety of purposes, but mainly for disinfection. The chemical properties of a biocide, as well as the biocide concentration, influence which cellular targets are affected. Exposure of bacteria to residual concentrations of biocides could lead to development of increased resistance towards the biocide in use, as well as cross-resistance towards other antimicrobials, including antibiotics. The aim of this study was to examine whether biocides could induce any potentially relevant genes that could affect pathogen's drug resistance or fitness. By examining global gene expression of the uropathogenic Escherichia coli CFT073 after exposure to subinhibitory concentrations of four biocides (benzalkonium chloride - BAC, chlorhexidine - CHX, hydrogen peroxide - H2O2, triclosan - TSN), we found that each biocide changed expression of different groups of genes and that exposure to benzalkonum chloride caused changes in expression of the largest number of genes among all biocides. In general, the four biocides tested in this study at subinhibitory concentrations did not increase the resistance potential of the pathogen to other antimicrobials. We could, however, identify clusters of genes that could possibly help the strain to grow in the presence of a biocide in the medium.
2019-12-05 | GSE135556 | GEO
Project description:The aim of this study was to characterise the transcriptomic changes in P. aeruginosa PA14 following treatment with antimicrobial manuka honey and its key components (sugar, methyglyoxal, sugar + methylglyoxal) for 30 minutes at a subinhibitory concentration (0.5x MIC). mRNA profiling was conducted to gain mechanistic insights into the mode of action of antimicrobial manuka honey.
2020-04-06 | GSE142448 | GEO
Project description:In this study, we monitored the transcriptional changes of S. aureus by RNA-seq analysis to better understand the effect of benzyl isothiocyanate (BITC) on the virulence inhibition of S. aureus and determined the bacteriostatic effect of BITC at subinhibitory concentrations. Our results revealed that compared with the control group (SAC), the BITC-treated experimental group (SAQ_BITC) had 708 differentially expressed genes (DEGs), of which 333 genes were downregulated and the capsular polysaccharide (cp) was significantly downregulated. Furthermore, we screened five of the most virulent factors of S. aureus, including the capsular polysaccharide biosynthesis protein (cp5D), capsular polysaccharide synthesis enzyme (cp8F), thermonuclease (nuc), clumping factor (clf) and protein A (spa).
2019-10-29 | GSE139494 | GEO
Project description:Biocides are chemical compounds widely used in hospital settings for a variety of purposes, but mainly for disinfection. The chemical properties of a biocide, as well as the biocide concentration, influence which cellular targets are affected. Exposure of bacteria to residual concentrations of biocides could lead to development of increased resistance towards the biocide in use, as well as cross-resistance towards other antimicrobials, including antibiotics. The aim of this study was to examine whether biocides could induce any potentially relevant genes that could affect pathogen's drug resistance or fitness. By examining global gene expression of the uropathogenic Escherichia coli CFT073 after exposure to subinhibitory concentrations of five biocides (benzalkonium chloride - BAC, chlorhexidine - CHX, ethanol - EtOH, hydrogen peroxide - H2O2, triclosan - TSN), we found that each biocide changed expression of different groups of genes and that exposure to ethanol caused changes in expression of the largest number of genes among all biocides. In general, the five biocides tested in this study at subinhibitory concentrations did not increase the resistance potential of the pathogen to other antimicrobials. We could, however, identify clusters of genes that could possibly help the strain to grow in the presence of a biocide in the medium. A culture of E. coli CFT073 without any biocide treatment served as the control sample. That culture was grown under the exact same conditions as the five biocide-treated samples. Each sample was collected in three biological replicates at the mid-exponential phase of growth.
2016-03-01 | E-GEOD-72738 | biostudies-arrayexpress