Response of Pseudomonas aeruginosa to the Innate Immune System-Derived Oxidants Hypochlorous Acid and Hypothiocyanous Acid

Farrant, Katie V.; Spiga, Livia; Davies, Jane C.; Williams, Huw D.

doi:10.1128/jb.00300-20

Cited by 24 publications

(36 citation statements)

References 98 publications

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“…3B-D). The activation of fro by NaOCl is consistent with a recent transcriptional study that identified fro as a gene that is upregulated by HOCl (18). We note that a higher concentration of 2 µM NaOCl did not increase fro expression.…”

Section: Fro Expression Is Induced By Hocl But Not By H2o2 or Hno3supporting

confidence: 92%

Activation of a bacterial flow sensor by hypochlorous acid from stimulated neutrophils

Foik

Urban

Huang

et al. 2022

Preprint

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Bacteria sense environmental stressors and activate responses to improve their survival in harsh growth conditions. Neutrophils respond to the presence of bacteria by producing oxidative antibacterial species including hypochlorous acid (HOCl). However, the extent that bacteria detect activated neutrophils or HOCl has not been known. Here, we report that the opportunistic bacterial pathogen Pseudomonas aeruginosa responds to activated neutrophils by activating the fro system, which regulates the expression of antioxidative factors. We show that this response is specific to HOCl and that other oxidative factors including H2O2, do not trigger a fro response. The fro system has been previously shown to detect flow that is present in host vasculature, such as in animal circulatory systems. Our data thus suggest a model in which fro serves as an early host detection system in P. aeruginosa that improves its survival against neutrophil-mediated defenses, which could promote colonization in human tissue and increase pathogenicity.

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Section: Fro Expression Is Induced By Hocl But Not By H2o2 or Hno3supporting

confidence: 92%

Activation of a bacterial flow sensor by hypochlorous acid from stimulated neutrophils

Foik

Urban

Huang

et al. 2022

Preprint

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“…Moreover, the expression of four previously characterized HOCl-stress defense systems was increased in CFT073 upon HOCl exposure (i.e. rclRABC, nemRA, cnoX, yedYZ) (26,27,(42)(43)(44). Our RNAseq analysis also revealed the upregulation of many biofilm genes in HOCl-stressed CFT073 (Fig.…”

Section: Hocl Causes Extensive Transcriptional Changes In Upecsupporting

confidence: 59%

Redox-mediated inactivation of the transcriptional repressor C3600 makes uropathogenicEscherichia coliexquisitely resistant to reactive chlorine species

Sultana¹,

LeDoux²,

Crompton³

et al. 2021

Preprint

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The ability to overcome stressful environments is critical for pathogen survival in the host. One challenge for bacteria is the exposure to reactive chlorine species (RCS), which are generated by innate immune cells as critical part of the oxidative burst. Hypochlorous acid (HOCl) is the most potent antimicrobial RCS and associated with extensive macromolecular damage in the phagocytized pathogen. However, bacteria have evolved defense strategies to alleviate the effects of HOCl-mediated damage. Among these are RCS-sensing transcriptional regulators that control the expression of HOCl-protective genes under non- and HOCl stress. Uropathogenic Escherichia coli (UPEC), the major causative agent of urinary tract infections (UTIs), is particularly exposed to infiltrating neutrophils during pathogenesis, however, their responses to and defenses of HOCl are still completely unexplored. Here, we present evidence that UPEC strains tolerate higher levels of HOCl and are better protected from neutrophil-mediated killing compared to other E. coli. Transcriptomic analysis of HOCl-stressed UPEC revealed the upregulation of an operon consisting of three genes, one of which encodes the transcriptional regulator C3600. We identified C3600 as a HOCl-sensing transcriptional repressor, which, under non-stress conditions, is bound to the operator and represses the expression of its target genes. During HOCl exposure, however, the repressor forms reversible intermolecular disulfide bonds and dissociates from the DNA resulting in the de-repression of the operon. Deletion of one of the target genes renders UPEC significantly more susceptible to HOCl indicating that the HOCl-mediated induction of the regulon plays a major role for UPEC’s HOCl resistance.

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“…It also plays important roles in DNA repair since it is located in an operon with the DNA helicase RecG [ 125 ]. In addition to the protection to H 2 O 2 , the oxyR-recG operon is also involved in P. aeruginosa protection against paraquat [ 125 ] and HOCl [ 109 ].…”

Section: Oxidative Stress Responses In P Aeruginosamentioning

confidence: 99%

“…IscR has been described to be involved in the stress response of P. aeruginosa to oxidative stress [ 109 , 207 , 210 ] and bacterial virulence [ 210 ]. iscR mutants presented lower KatA, SodA, and SodB production than the wild-type [ 207 , 210 ], and this gene was required for the activity of KatA at the post-translational level [ 210 ].…”

Section: Oxidative Stress Responses In P Aeruginosamentioning

confidence: 99%

“…They found that 70% of the genes upregulated by HOSCN were also induced by NaOCl, indicating that different agents share many bacterial stress responses. These genes belong to the noncoding RNA, protein secretion/export apparatus, and antibiotic resistance and susceptibility [109]. In the study conducted by Groitl et al (2017), the authors analyzed gene expression changes of P. aeruginosa PA14 treated with HOCl, HOBr, and HOSCN.…”

Section: Evaluation Of Oxidative Stress Responses Of P Aeruginosa By Transcriptomic Studiesmentioning

confidence: 99%

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Oxidative Stress Response in Pseudomonas aeruginosa

et al. 2021

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Pseudomonas aeruginosa is a Gram-negative environmental and human opportunistic pathogen highly adapted to many different environmental conditions. It can cause a wide range of serious infections, including wounds, lungs, the urinary tract, and systemic infections. The high versatility and pathogenicity of this bacterium is attributed to its genomic complexity, the expression of several virulence factors, and its intrinsic resistance to various antimicrobials. However, to thrive and establish infection, P. aeruginosa must overcome several barriers. One of these barriers is the presence of oxidizing agents (e.g., hydrogen peroxide, superoxide, and hypochlorous acid) produced by the host immune system or that are commonly used as disinfectants in a variety of different environments including hospitals. These agents damage several cellular molecules and can cause cell death. Therefore, bacteria adapt to these harsh conditions by altering gene expression and eliciting several stress responses to survive under oxidative stress. Here, we used PubMed to evaluate the current knowledge on the oxidative stress responses adopted by P. aeruginosa. We will describe the genes that are often differently expressed under oxidative stress conditions, the pathways and proteins employed to sense and respond to oxidative stress, and how these changes in gene expression influence pathogenicity and the virulence of P. aeruginosa. Understanding these responses and changes in gene expression is critical to controlling bacterial pathogenicity and developing new therapeutic agents.

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Response of Pseudomonas aeruginosa to the Innate Immune System-Derived Oxidants Hypochlorous Acid and Hypothiocyanous Acid

Cited by 24 publications

References 98 publications

Activation of a bacterial flow sensor by hypochlorous acid from stimulated neutrophils

Activation of a bacterial flow sensor by hypochlorous acid from stimulated neutrophils

Redox-mediated inactivation of the transcriptional repressor C3600 makes uropathogenicEscherichia coliexquisitely resistant to reactive chlorine species

Oxidative Stress Response in Pseudomonas aeruginosa

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