Interaction of RecA mediated SOS response with bacterial persistence, biofilm formation, and host response

Kaushik, Vaishali; Tiwari, Monalisa; Tiwari, Vishvanath

doi:10.1016/j.ijbiomac.2022.07.176

Cited by 32 publications

(16 citation statements)

References 176 publications

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“…We also observed the increased expression of pgaB and the gene coding for UDP-N-acetylglucosamine acyltransferase (novel00626) in biofilm cells exposed to sub-MICs of imipenem and colistin. This observation explains how sub-MICs of antimicrobials enhance biofilm formation which was described in a previous in-vitro study [ 16 , 25 ]. The biofilm matrix formation triggers stress-induced metabolic or transcriptional changes that increase resistance in cells exposed to sub-MICs of antibiotics [ 26 , 27 ].…”

Section: Discussionsupporting

confidence: 76%

Effects of Sub-Minimum Inhibitory Concentrations of Imipenem and Colistin on Expression of Biofilm-Specific Antibiotic Resistance and Virulence Genes in Acinetobacter baumannii Sequence Type 1894

Shenkutie

Zhang

Yao

et al. 2022

IJMS

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Antibiotics at suboptimal doses promote biofilm formation and the development of antibiotic resistance. The underlying molecular mechanisms, however, were not investigated. Here, we report the effects of sub-minimum inhibitory concentrations (sub-MICs) of imipenem and colistin on genes associated with biofilm formation and biofilm-specific antibiotic resistance in a multidrug-tolerant clinical strain of Acinetobacter baumannii Sequence Type (ST) 1894. Comparative transcriptome analysis was performed in untreated biofilm and biofilm treated with sub-MIC doses of imipenem and colistin. RNA sequencing data showed that 78 and 285 genes were differentially expressed in imipenem and colistin-treated biofilm cells, respectively. Among the differentially expressed genes (DEGs), 48 and 197 genes were upregulated exclusively in imipenem and colistin-treated biofilm cells, respectively. The upregulated genes included those encoding matrix synthesis (pgaB), multidrug efflux pump (novel00738), fimbrial proteins, and homoserine lactone synthase (AbaI). Upregulation of biofilm-associated genes might enhance biofilm formation when treated with sub-MICs of antibiotics. The downregulated genes include those encoding DNA gyrase (novel00171), 30S ribosomal protein S20 (novel00584), and ribosome releasing factor (RRF) were downregulated when the biofilm cells were treated with imipenem and colistin. Downregulation of these genes affects protein synthesis, which in turn slows down cell metabolism and makes biofilm cells more tolerant to antibiotics. In this investigation, we also found that 5 of 138 small RNAs (sRNAs) were differentially expressed in biofilm regardless of antibiotic treatment or not. Of these, sRNA00203 showed the highest expression levels in biofilm. sRNAs regulate gene expression and are associated with biofilm formation, which may in turn affect the expression of biofilm-specific antibiotic resistance. In summary, when biofilm cells were exposed to sub-MIC doses of colistin and imipenem, coordinated gene responses result in increased biofilm production, multidrug efflux pump expression, and the slowdown of metabolism, which leads to drug tolerance in biofilm. Targeting antibiotic-induced or repressed biofilm-specific genes represents a new strategy for the development of innovative and effective treatments for biofilm-associated infections caused by A. baumannii.

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Section: Discussionsupporting

confidence: 76%

Effects of Sub-Minimum Inhibitory Concentrations of Imipenem and Colistin on Expression of Biofilm-Specific Antibiotic Resistance and Virulence Genes in Acinetobacter baumannii Sequence Type 1894

Shenkutie

Zhang

Yao

et al. 2022

IJMS

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“…Many recent articles have noted that extracellular DNA plays an important role in the formation of biofilms, including in pathogenic bacteria [ 30 , 39 , 40 , 41 ]. A smaller number of articles have shown that the SOS response also promotes the formation of bacterial biofilms [ 42 , 43 ], but those reports did not recognize that the two phenomena are linked. Our results reported here, therefore, provide a bridge between these two areas of investigation because the SOS-inducing drugs actually trigger the release of extracellular DNA.…”

Section: Discussionmentioning

confidence: 99%

Role of Extracellular DNA in Bacterial Response to SOS-Inducing Drugs

Crane

Catanzaro²

2023

Antibiotics

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The SOS response is a conserved stress response pathway that is triggered by DNA damage in the bacterial cell. Activation of this pathway can, in turn, cause the rapid appearance of new mutations, sometimes called hypermutation. We compared the ability of various SOS-inducing drugs to trigger the expression of RecA, cause hypermutation, and produce elongation of bacteria. During this study, we discovered that these SOS phenotypes were accompanied by the release of large amounts of DNA into the extracellular medium. The release of DNA was accompanied by a form of bacterial aggregation in which the bacteria became tightly enmeshed in DNA. We hypothesize that DNA release triggered by SOS-inducing drugs could promote the horizontal transfer of antibiotic resistance genes by transformation or by conjugation.

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“…It is known that RecA is the main component of the cellular SOS stress response, which activates multiple genes involved in DNA repair. Additionally, RecA has been implicated in swarming motility (Gomez-Gomez et al, 2007), adhesion to surfaces (Costa et al, 2014) and biofilm formation (Kaushik et al, 2022), which may affect cell envelope mechanics and expression of mechanosensitive channels. We hypothesize that deletion of recA may silence the expression of residual MscS-like channels, which normally (in MJF429) would provide additional permeability and quickly deactivate MscL after the shock.…”

Section: Quantitative Treatment Of Scattering Tracesmentioning

confidence: 99%

Mechanosensitive channel MscS is critical for termination of the bacterial hypoosmotic permeability response

Moller

Britt

Schams

et al. 2023

Preprint

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Free-living microorganisms are subjected to drastic changes in osmolarity. To avoid lysis under sudden osmotic down-shock, bacteria quickly expel small metabolites through the tension-activated channels MscL, MscS, and MscK. We examined five chromosomal knockout strains, ΔmscL, ΔmscS, a double knockout ΔmscSΔmscK, and a triple knockout ΔmscLΔmscSΔmscKin comparison to the wild-type parental strain. Stopped-flow experiments confirmed that both MscS and MscL mediate fast osmolyte release and curb cell swelling, but osmotic viability assays indicated that they are not equivalent. MscS alone was capable of rescuing the cell population, but in some strains MscL did not rescue and additionally became toxic in the absence of both MscS and MscK. Furthermore, MscS was upregulated in the ΔmscLstrain, suggesting either a cross-talk between the two genes/proteins or the influence of cell mechanics onmscSexpression. The data shows that for the proper termination of the permeability response, the high-threshold (MscL) and the low-threshold (MscS/MscK) channels must act sequentially. In the absence of low-threshold channels, at the end of the release phase, MscL should stabilize membrane tension at around 10 mN/m. Patch-clamp protocols emulating the tension changes during the release phase indicated that the non-inactivating MscL, residing at its own tension threshold, flickers and produces a protracted leakage. The MscS/MscK population, when present, stays open at this stage to reduce tension below the MscL threshold and silence the large channel. When MscS reaches its own threshold, it inactivates and thus ensures proper termination of the hypoosmotic permeability response. This functional interplay between the high- and low-threshold channels is further supported by the compromised osmotic survival of bacteria expressing non-inactivating MscS mutants.Summary (for the table of contents)The kinetics of hypotonic osmolyte release fromE. coliis analyzed in conjunction with bacterial survival. It is shown that MscL, the high-threshold ‘emergency release valve’, rescues bacteria from down-shocks only in the presence of MscS, MscK or other low-threshold channels that are necessary to pacify MscL at the end of the release phase.

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Interaction of RecA mediated SOS response with bacterial persistence, biofilm formation, and host response

Cited by 32 publications

References 176 publications

Effects of Sub-Minimum Inhibitory Concentrations of Imipenem and Colistin on Expression of Biofilm-Specific Antibiotic Resistance and Virulence Genes in Acinetobacter baumannii Sequence Type 1894

Effects of Sub-Minimum Inhibitory Concentrations of Imipenem and Colistin on Expression of Biofilm-Specific Antibiotic Resistance and Virulence Genes in Acinetobacter baumannii Sequence Type 1894

Role of Extracellular DNA in Bacterial Response to SOS-Inducing Drugs

Mechanosensitive channel MscS is critical for termination of the bacterial hypoosmotic permeability response

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