Achromobacter spp. genetic adaptation in cystic fibrosis

Achromobacter spp. are emerging pathogens in patients with cystic fibrosis (CF) and Achromobacter spp. caused infections are associated with more severe disease outcomes and high intrinsic antibiotic resistance. While conventional CF pathogens are studied extensively, little is known about the genetic determinants leading to antibiotic resistance and the genetic adaptation in Achromobacter spp. infections. Here, we analysed 101 Achromobacter spp. genomes from 51 patients with CF isolated during the course of up to 20 years of infection to identify within-host adaptation, mutational signatures and genetic variation associated with increased antibiotic resistance. We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and between Achromobacter species, indicating convergent genetic adaptation. Genome-wide association study of six antibiotic resistance phenotypes revealed the enrichment of associated genes involved in inorganic ion transport, transcription gene enrichment in β-lactams, and energy production and translation gene enrichment in the trimethoprim/sulfonamide group. Overall, we provide insights into the pathogenomics of Achromobacter spp. infections in patients with CF airways. Since emerging pathogens are increasingly recognized as an important healthcare issue, our findings on evolution of antibiotic resistance and genetic adaptation can facilitate better understanding of disease progression and how mutational changes have implications for patients with CF.

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Achromobacter genetic adaptation in cystic fibrosis

10.1101/2021.01.13.426490 ◽

2021 ◽

Author(s):

Migle Gabrielaite ◽

Finn C. Nielsen ◽

Helle K. Johansen ◽

Rasmus L. Marvig

Keyword(s):

Cystic Fibrosis ◽

Antibiotic Resistance ◽

Ion Transport ◽

Genome Wide Association Study ◽

Severe Disease ◽

Genetic Adaptation ◽

Emerging Pathogens ◽

Inorganic Ion ◽

Gene Enrichment ◽

Genome Wide

AbstractAchromobacter is an emerging pathogen in patients with cystic fibrosis (CF) and Achromobacter caused infections are associated with more severe disease outcomes and high intrinsic antibiotic resistance. While conventional CF pathogens are studied extensively, little is known about the genetic determinants leading to antibiotic resistance and the genetic adaptation in Achromobacter infections.Here, we analyzed 101 Achromobacter genomes from 51 patients with CF isolated during the course of up to 20 years of infection to identify within-host adaptation, mutational signatures, and genetic variation associated with increased antibiotic resistance.We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and between Achromobacter species indicating convergent genetic adaptation. Genome-wide association study (GWAS) of six antibiotic resistance phenotypes revealed the enrichment of associated genes involved in inorganic ion transport genes, transcription gene enrichment in β-lactams, and energy production and translation gene enrichment in the trimethoprim/sulfonamide group.Overall, we provide insights into the pathogenomics of Achromobacter infections in patients with CF airways. Since emerging pathogens are increasingly recognised as an important healthcare issue, our findings on evolution of antibiotic resistance and genetic adaptation can facilitate better understanding of disease progression and how mutational changes have implications for patients with CF.

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Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization

Journal of Medical Microbiology ◽

10.1099/jmm.0.001281 ◽

2020 ◽

Author(s):

Eliana Alcaraz ◽

Daniela Centrón ◽

Gabriela Camicia ◽

María Paula Quiroga ◽

José Di Conza ◽

...

Keyword(s):

Cystic Fibrosis ◽

Adult Patient ◽

Virulence Factors ◽

Stenotrophomonas Maltophilia ◽

Type Species ◽

Mutation Frequency ◽

Content Type ◽

Link Type ◽

Clonal Relatedness ◽

Over Time

Introduction. Stenotrophomonas maltophilia has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Hypothesis. Sequential isolates of S. maltophilia from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. Aim. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential S. maltophilia isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. Methodology. The antibiotic resistance of 11 S. maltophilia isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Results. Seven S. maltophilia isolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. XbaI PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified stmPr1 and stmPr2 genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. Conclusion. The present study shows the long-time persistence of two related S. maltophilia clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.

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Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus

Journal of Medical Microbiology ◽

10.1099/jmm.0.001467 ◽

2022 ◽

Vol 71 (1) ◽

Author(s):

Bailey F. Keefe ◽

Luiz E. Bermudez

Keyword(s):

Cystic Fibrosis ◽

Host Cell ◽

Biofilm Formation ◽

Type Species ◽

Divalent Cations ◽

Mycobacterium Abscessus ◽

Content Type ◽

Link Type ◽

Populations At Risk

Introduction. Pulmonary infections caused by organisms of the Mycobacterium abscessus complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema. Hypothesis. M. abscessus infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis. Aim. Evaluate the ability of M. abscessus to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients. Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA. Results. M. abscessus is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. M. abscessus also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear. Conclusions. In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate M. abscessus establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

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Fis Contributes to Resistance of Pseudomonas aeruginosa to Ciprofloxacin by Regulating Pyocin Synthesis

Journal of Bacteriology ◽

10.1128/jb.00064-20 ◽

2020 ◽

Vol 202 (11) ◽

Cited By ~ 1

Author(s):

Yuqing Long ◽

Weixin Fu ◽

Su Wang ◽

Xuan Deng ◽

Yongxin Jin ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Bacterial Resistance ◽

Global Gene Expression ◽

Chronic Infections ◽

Mobility Shift ◽

Content Type ◽

Regulatory Pathways ◽

Opportunistic Pathogenic

ABSTRACT Factor for inversion stimulation (Fis) is a versatile DNA binding protein that plays an important role in coordinating bacterial global gene expression in response to growth phases and environmental stresses. Previously, we demonstrated that Fis regulates the type III secretion system (T3SS) in Pseudomonas aeruginosa. In this study, we explored the role of Fis in the antibiotic resistance of P. aeruginosa and found that mutation of the fis gene increases the bacterial susceptibility to ciprofloxacin. We further demonstrated that genes related to pyocin biosynthesis are upregulated in the fis mutant. The pyocins are produced in response to genotoxic agents, including ciprofloxacin, and the release of pyocins results in lysis of the producer cell. Thus, pyocin biosynthesis genes sensitize P. aeruginosa to ciprofloxacin. We found that PrtN, the positive regulator of the pyocin biosynthesis genes, is upregulated in the fis mutant. Genetic experiments and electrophoretic mobility shift assays revealed that Fis directly binds to the promoter region of prtN and represses its expression. Therefore, our results revealed novel Fis-mediated regulation on pyocin production and bacterial resistance to ciprofloxacin in P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is an important opportunistic pathogenic bacterium that causes various acute and chronic infections in human, especially in patients with compromised immunity, cystic fibrosis (CF), and/or severe burn wounds. About 60% of cystic fibrosis patients have a chronic respiratory infection caused by P. aeruginosa. The bacterium is intrinsically highly resistant to antibiotics, which greatly increases difficulties in clinical treatment. Therefore, it is critical to understand the mechanisms and the regulatory pathways that are involved in antibiotic resistance. In this study, we elucidated a novel regulatory pathway that controls the bacterial resistance to fluoroquinolone antibiotics, which enhances our understanding of how P. aeruginosa responds to ciprofloxacin.

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Pseudomonas aeruginosa Alginate Benefits Staphylococcus aureus?

Journal of Bacteriology ◽

10.1128/jb.00040-20 ◽

2020 ◽

Vol 202 (8) ◽

Cited By ~ 1

Author(s):

Michael J. Schurr

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Cell Membrane ◽

Membrane Integrity ◽

Partial Explanation ◽

Content Type ◽

First Report ◽

Cell Membrane Integrity ◽

Link Type

ABSTRACT In this issue of Journal of Bacteriology, Price et al. show that the Pseudomonas aeruginosa-produced exopolysaccharide alginate protects Staphylococcus aureus by dampening the expression of P. aeruginosa virulence products that usually inhibit S. aureus respiration and cell membrane integrity when the two organisms compete in other environments (C. E. Price, D. G. Brown, D. H. Limoli, V. V. Phelan, and G. A. O’Toole, J Bacteriol 202:e00559-19, 2020, https://doi.org/10.1128/jb.00559-19). This is the first report that exogenously added alginate affects P. aeruginosa competition and provides a partial explanation for S. aureus and P. aeruginosa coinfections in cystic fibrosis.

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Prevalence of Mycoplasma genitalium fluoroquinolone-resistance markers, and dual-class-resistance markers, in asymptomatic men who have sex with men

Journal of Medical Microbiology ◽

10.1099/jmm.0.001429 ◽

2021 ◽

Vol 70 (9) ◽

Author(s):

Teck-Phui Chua ◽

Kaveesha Bodiyabadu ◽

Dorothy A. Machalek ◽

Suzanne M. Garland ◽

Catriona S. Bradshaw ◽

...

Keyword(s):

Antibiotic Resistance ◽

Type Species ◽

Health Centre ◽

Mycoplasma Genitalium ◽

Fluoroquinolone Resistance ◽

Content Type ◽

Link Type ◽

Resistance Markers ◽

Sex With Men ◽

Dual Class

Introduction. Failure of fluoroquinolones, the principal treatment option for macrolide-resistant Mycoplasma genitalium infections, has recently emerged. This is of particular concern for men who have sex with men (MSM), who have high proportions of macrolide-resistant M. genitalium infections. Treatment failure with moxifloxacin is likely the result of single nucleotide polymorphisms (SNPs) in parC, whilst concurrent gyrA mutations may play a role. Gap Statement. The levels of fluoroquinolone resistance and dual-class (i.e. macrolide and fluoroquinolone) resistance in M. genitalium among asymptomatic MSM is unknown. Aim. To (i) determine the proportion of fluoroquinolone resistance and dual-class resistance in M. genitalium infections among asymptomatic MSM, (ii) explore any clinical and behavioural associations with fluoroquinolone resistance, and (iii) determine the distribution of antibiotic resistance among M. genitalium mgpB sequence types (STs). Methodology. M. genitalium positive samples (N=94) were obtained from 1001 asymptomatic MSM enrolled in a study at Melbourne Sexual Health Centre (Carlton, Australia) between August 2016 and September 2017. Sanger sequencing was performed to determine the proportion of M. genitalium infections with SNPs in parC that have previously been associated with failure of moxifloxacin (corresponding to amino changes S83I, D83R, D87Y and D87N) and in gyrA (corresponding to amino acid changes M95I, D99N, D99Y and D99G). Associations between clinical/behavioural factors and parC SNPs were examined. Strain typing was performed by sequencing a portion of the mgpB gene. Results. The proportion of MSM with infections harbouring parC and gyrA SNPs was 13.0 % [95 % confidence interval (CI): 6.8–23.2 %] and 4.7 % (95 % CI: 1.1–13.4 %), respectively; dual-class resistance was 13.0 %. No significant clinical/behavioural associations were found. Antibiotic resistance was not restricted to specific mgpB STs. Conclusion. One in eight (13 %) of asymptomatic MSM with M. genitalium had an infection with dual-class-resistance mutations. Typing by mgpB sequence suggested fluoroquinolone resistance is arising from independent mutation events. This study illustrates that asymptomatic MSM may act as a reservoir for antibiotic-resistant M. genitalium .

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bla OXA-48-like genome architecture among carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in the Netherlands

Microbial Genomics ◽

10.1099/mgen.0.000512 ◽

2021 ◽

Vol 7 (5) ◽

Author(s):

Antoni P. A. Hendrickx ◽

Fabian Landman ◽

Angela de Haan ◽

Sandra Witteveen ◽

Marga G. van Santen-Verheuvel ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

The Netherlands ◽

Resistance Genes ◽

Type Species ◽

Antibiotic Resistance Genes ◽

Gene Content ◽

Content Type ◽

E Coli ◽

Link Type

Carbapenem-hydrolysing enzymes belonging to the OXA-48-like group are encoded by bla OXA-48-like alleles and are abundant among Enterobacterales in the Netherlands. Therefore, the objective here was to investigate the characteristics, gene content and diversity of the bla OXA-48-like carrying plasmids and chromosomes of Escherichia coli and Klebsiella pneumoniae collected in the Dutch national surveillance from 2014 to 2019 in comparison with genome sequences from 29 countries. A combination of short-read genome sequencing with long-read sequencing enabled the reconstruction of 47 and 132 complete bla OXA-48-like plasmids for E. coli and K. pneumoniae , respectively. Seven distinct plasmid groups designated as pOXA-48-1 to pOXA-48-5, pOXA-181 and pOXA-232 were identified in the Netherlands which were similar to internationally reported plasmids obtained from countries from North and South America, Europe, Asia and Oceania. The seven plasmid groups varied in size, G+C content, presence of antibiotic resistance genes, replicon family and gene content. The pOXA-48-1 to pOXA-48-5 plasmids were variable, and the pOXA-181 and pOXA-232 plasmids were conserved. The pOXA-48-1, pOXA-48-2, pOXA-48-3 and pOXA-48-5 groups contained a putative conjugation system, but this was absent in the pOXA-48-4, pOXA-181 and pOXA-232 plasmid groups. pOXA-48 plasmids contained the PemI antitoxin, while the pOXA-181 and pOXA-232 plasmids did not. Furthermore, the pOXA-181 plasmids carried a virB2-virB3-virB9-virB10-virB11 type IV secretion system, while the pOXA-48 plasmids and pOXA-232 lacked this system. A group of non-related pOXA-48 plasmids from the Netherlands contained different resistance genes, non-IncL-type replicons or no replicons. Whole genome multilocus sequence typing revealed that the bla OXA-48-like plasmids were found in a wide variety of genetic backgrounds in contrast to chromosomally encoded bla OXA-48-like alleles. Chromosomally localized bla OXA-48 and bla OXA-244 alleles were located on genetic elements of variable sizes and comprised regions of pOXA-48 plasmids. The bla OXA-48-like genetic element was flanked by a direct repeat upstream of IS1R, and was found at multiple locations in the chromosomes of E. coli . Lastly, K. pneumoniae isolates carrying bla OXA-48 or bla OXA-232 were mostly resistant for meropenem, whereas E. coli bla OXA-48, bla OXA-181 and chromosomal bla OXA-48 or bla OXA-244 isolates were mostly sensitive. In conclusion, the overall bla OXA-48-like plasmid population in the Netherlands is conserved and similar to that reported for other countries, confirming global dissemination of bla OXA-48-like plasmids. Variations in size, presence of antibiotic resistance genes and gene content impacted pOXA-48, pOXA-181 and pOXA-232 plasmid architecture.

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Phylum barrier and Escherichia coli intra-species phylogeny drive the acquisition of antibiotic-resistance genes

Microbial Genomics ◽

10.1099/mgen.0.000489 ◽

2021 ◽

Vol 7 (8) ◽

Author(s):

Marie Petitjean ◽

Bénédicte Condamine ◽

Charles Burdet ◽

Erick Denamur ◽

Etienne Ruppé

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Resistance Genes ◽

Type Species ◽

Antibiotic Resistance Genes ◽

Resistance Pattern ◽

Content Type ◽

E Coli ◽

Link Type ◽

Specific Distribution

Escherichia coli is a ubiquitous bacterium that has been widely exposed to antibiotics over the last 70 years. It has adapted by acquiring different antibiotic-resistance genes (ARGs), the census of which we aim to characterize here. To do so, we analysed 70 301 E. coli genomes obtained from the EnteroBase database and detected 1 027 651 ARGs using the AMRFinder, Mustard and ResfinderFG ARG databases. We observed a strong phylogroup and clonal lineage specific distribution of some ARGs, supporting the argument for epistasis between ARGs and the strain genetic background. However, each phylogroup had ARGs conferring a similar antibiotic class resistance pattern, indicating phenotypic adaptive convergence. The G+C content or the type of ARG was not associated with the frequency of the ARG in the database. In addition, we identified ARGs from anaerobic, non- Proteobacteria bacteria in four genomes of E. coli , supporting the hypothesis that the transfer between anaerobic bacteria and E. coli can spontaneously occur but remains exceptional. In conclusion, we showed that phylum barrier and intra-species phylogenetic history are major drivers of the acquisition of a resistome in E. coli .

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Horizontal Gene Transfer of Antibiotic Resistance from Acinetobacter baylyi to Escherichia coli on Lettuce and Subsequent Antibiotic Resistance Transmission to the Gut Microbiome

mSphere ◽

10.1128/msphere.00329-20 ◽

2020 ◽

Vol 5 (3) ◽

Cited By ~ 2

Author(s):

Marlène Maeusli ◽

Bosul Lee ◽

Sarah Miller ◽

Zeferino Reyna ◽

Peggy Lu ◽

...

Keyword(s):

Antibiotic Resistance ◽

Gene Transfer ◽

Horizontal Gene Transfer ◽

Resistance Genes ◽

Gut Microbiome ◽

Acinetobacter Baylyi ◽

Antibiotic Resistant ◽

Content Type ◽

Plant Foods ◽

Link Type

ABSTRACT Agricultural use of antibiotics is recognized by the U.S. Centers for Disease Control and Prevention as a major contributor to antibiotic-resistant infections. While most One Health attention has been on the potential for antibiotic resistance transmission from livestock and contaminated meat products to people, plant foods are fundamental to the food chain for meat eaters and vegetarians alike. We hypothesized that environmental bacteria that colonize plant foods may serve as platforms for the persistence of antibiotic-resistant bacteria and for horizontal gene transfer of antibiotic-resistant genes. Donor Acinetobacter baylyi and recipient Escherichia coli were cocultured in vitro, in planta on lettuce, and in vivo in BALB/c mice. We showed that nonpathogenic, environmental A. baylyi is capable of transferring plasmids conferring antibiotic resistance to E. coli clinical isolates on lettuce leaf discs. Furthermore, transformant E. coli from the in planta assay could then colonize the mouse gut microbiome. The target antibiotic resistance plasmid was identified in mouse feces up to 5 days postinfection. We specifically identified in vivo transfer of the plasmid to resident Klebsiella pneumoniae in the mouse gut. Our findings highlight the potential for environmental bacteria exposed to antibiotics to transmit resistance genes to mammalian pathogens during ingestion of leafy greens. IMPORTANCE Previous efforts have correlated antibiotic-fed livestock and meat products with respective antibiotic resistance genes, but virtually no research has been conducted on the transmission of antibiotic resistance from plant foods to the mammalian gut (C. S. Hölzel, J. L. Tetens, and K. Schwaiger, Pathog Dis 15:671–688, 2018, https://doi.org/10.1089/fpd.2018.2501; C. M. Liu et al., mBio 9:e00470-19, 2018, https://doi.org/10.1128/mBio.00470-18; B. Spellberg et al., NAM Perspectives, 2016, https://doi.org/10.31478/201606d; J. O’Neill, Antimicrobials in agriculture and the environment, 2015; Centers for Disease Control and Prevention, Antibiotic resistance threats in the United States, 2019). Here, we sought to determine if horizontal transmission of antibiotic resistance genes can occur between lettuce and the mammalian gut microbiome, using a mouse model. Furthermore, we have created a new model to study horizontal gene transfer on lettuce leaves using an antibiotic-resistant transformant of A. baylyi (AbzeoR).

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

Journal of Bacteriology ◽

10.1128/jb.00300-20 ◽

2020 ◽

Vol 203 (2) ◽

pp. e00300-20

Author(s):

Katie V. Farrant ◽

Livia Spiga ◽

Jane C. Davies ◽

Huw D. Williams

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Antibiotic Resistance ◽

Immune System ◽

Hypochlorous Acid ◽

Secretion System ◽

Content Type ◽

Type 3 Secretion System ◽

Lung Infections ◽

Type 3

ABSTRACTPseudomonas aeruginosa is a significant nosocomial pathogen and is associated with lung infections in cystic fibrosis (CF). Once established, P. aeruginosa infections persist and are rarely eradicated despite host immune cells producing antimicrobial oxidants, including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). There is limited knowledge as to how P. aeruginosa senses, responds to, and protects itself against HOCl and HOSCN and the contribution of such responses to its success as a CF pathogen. To investigate the P. aeruginosa response to these oxidants, we screened 707 transposon mutants, with mutations in regulatory genes, for altered growth following HOCl exposure. We identified regulators of antibiotic resistance, methionine biosynthesis, catabolite repression, and PA14_07340, the homologue of the Escherichia coli HOCl-sensor RclR (30% identical), which are required for protection against HOCl. We have shown that RclR (PA14_07340) protects specifically against HOCl and HOSCN stress and responds to both oxidants by upregulating the expression of a putative peroxiredoxin, rclX (PA14_07355). Transcriptional analysis revealed that while there was specificity in the response to HOCl (231 genes upregulated) and HOSCN (105 genes upregulated), there was considerable overlap, with 74 genes upregulated by both oxidants. These included genes encoding the type 3 secretion system, sulfur and taurine transport, and the MexEF-OprN efflux pump. RclR coordinates part of the response to both oxidants, including upregulation of pyocyanin biosynthesis genes, and, in the presence of HOSCN, downregulation of chaperone genes. These data indicate that the P. aeruginosa response to HOCl and HOSCN is multifaceted, with RclR playing an essential role.IMPORTANCE The bacterial pathogen Pseudomonas aeruginosa causes devastating infections in immunocompromised hosts, including chronic lung infections in cystic fibrosis patients. To combat infection, the host’s immune system produces the antimicrobial oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). Little is known about how P. aeruginosa responds to and survives attack from these oxidants. To address this, we carried out two approaches: a mutant screen and transcriptional study. We identified the P. aeruginosa transcriptional regulator, RclR, which responds specifically to HOCl and HOSCN stress and is essential for protection against both oxidants. We uncovered a link between the P. aeruginosa transcriptional response to these oxidants and physiological processes associated with pathogenicity, including antibiotic resistance and the type 3 secretion system.

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