Bacterial Stress Response Mechanisms: Signal Perception, Transduction and Adaptation

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 49608

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Laboratoire de Microbiologie Signaux et Microenvironnement, LMSM EA4312, Université de Rouen Normandie, IUT Evreux - 55 rue St Germain, 27000 Evreux, France
Interests: bacterial stress response; adaptation; biofilm and virulence; antimicrobial strategies
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Guest Editor
Normandie Sécurité Sanitaire, Université de Rouen Normandie, IUT Evreux - 55 rue St Germain, 27000 Evreux, France
Interests: Pseudomonas aeruginosa; microbial persistence; microbial molecular biology; microbiology; antimicrobial strategies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In their natural habitats, bacteria are exposed to changing and challenging environmental conditions that are perceived as stresses, to which they need to adapt to ensure their survival. Pathogens, in particular, must be able to overcome various host defense mechanisms. To cope with stress, bacteria have evolved intricate systems known as stress response, which sense these changes and rapidly trigger the well-orchestrated reprogramming of the expression of specific genes, leading to the production of effectors and allowing their survival and dissemination under these conditions. Stress response regulation involves several molecular pathways at the levels of transcription, translation, and stability of transcripts and of proteins. A better understanding of these stress response mechanisms may be useful for developing new strategies to fight bacteria that, in some cases, represent an important life threat.

This Special Issue aims to showcase our increased understanding of the mechanisms by which bacteria sense and respond to stresses encountered in the host or other environments.

Potential topics include, but are not limited to the following:

  • Bacterial stress response;
  • Molecular mechanisms involved in bacterial adaptation;
  • Response to antimicrobials, host immune system, hormones, and environmental cues;
  • Response to antimicrobial potentiators;
  • Sigma factors, TCS, sncRNA.
Prof. Dr. Sylvie Chevalier
Prof. Dr. Pierre Cornelis
Guest Editors

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Keywords

  • adaptation
  • signal perception and transduction
  • regulation networks

Published Papers (12 papers)

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Research

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19 pages, 4319 KiB  
Article
Effect of Phthalates and Their Substitutes on the Physiology of Pseudomonas aeruginosa
by Mélissande Louis, Ali Tahrioui, Julien Verdon, Audrey David, Sophie Rodrigues, Magalie Barreau, Maëliss Manac’h, Audrey Thiroux, Baptiste Luton, Charly Dupont, Marie Le Calvé, Alexis Bazire, Alexandre Crépin, Maximilien Clabaut, Emilie Portier, Laure Taupin, Florian Defontaine, Thomas Clamens, Emeline Bouffartigues, Pierre Cornelis, Marc Feuilloley, Jocelyne Caillon, Alain Dufour, Jean-Marc Berjeaud, Olivier Lesouhaitier and Sylvie Chevalieradd Show full author list remove Hide full author list
Microorganisms 2022, 10(9), 1788; https://doi.org/10.3390/microorganisms10091788 - 5 Sep 2022
Cited by 4 | Viewed by 2060
Abstract
Phthalates are used in a variety of applications—for example, as plasticizers in polyvinylchloride products to improve their flexibility—and can be easily released into the environment. In addition to being major persistent organic environmental pollutants, some phthalates are responsible for the carcinogenicity, teratogenicity, and [...] Read more.
Phthalates are used in a variety of applications—for example, as plasticizers in polyvinylchloride products to improve their flexibility—and can be easily released into the environment. In addition to being major persistent organic environmental pollutants, some phthalates are responsible for the carcinogenicity, teratogenicity, and endocrine disruption that are notably affecting steroidogenesis in mammals. Numerous studies have thus focused on deciphering their effects on mammals and eukaryotic cells. While multicellular organisms such as humans are known to display various microbiota, including all of the microorganisms that may be commensal, symbiotic, or pathogenic, few studies have aimed at investigating the relationships between phthalates and bacteria, notably regarding their effects on opportunistic pathogens and the severity of the associated pathologies. Herein, the effects of phthalates and their substitutes were investigated on the human pathogen, Pseudomonas aeruginosa, in terms of physiology, virulence, susceptibility to antibiotics, and ability to form biofilms. We show in particular that most of these compounds increased biofilm formation, while some of them enhanced the bacterial membrane fluidity and altered the bacterial morphology. Full article
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16 pages, 2205 KiB  
Article
RNase III Participates in the Adaptation to Temperature Shock and Oxidative Stress in Escherichia coli
by Maxence Lejars and Eliane Hajnsdorf
Microorganisms 2022, 10(4), 699; https://doi.org/10.3390/microorganisms10040699 - 24 Mar 2022
Cited by 3 | Viewed by 2514
Abstract
Bacteria thrive in ever-changing environments by quickly remodeling their transcriptome and proteome via complex regulatory circuits. Regulation occurs at multiple steps, from the transcription of genes to the post-translational modification of proteins, via both protein and RNA regulators. At the post-transcriptional level, the [...] Read more.
Bacteria thrive in ever-changing environments by quickly remodeling their transcriptome and proteome via complex regulatory circuits. Regulation occurs at multiple steps, from the transcription of genes to the post-translational modification of proteins, via both protein and RNA regulators. At the post-transcriptional level, the RNA fate is balanced through the binding of ribosomes, chaperones and ribonucleases. We aim to decipher the role of the double-stranded-RNA-specific endoribonuclease RNase III and to evaluate its biological importance in the adaptation to modifications of the environment. The inactivation of RNase III affects a large number of genes and leads to several phenotypical defects, such as reduced thermotolerance in Escherichia coli. In this study, we reveal that RNase III inactivation leads to an increased sensitivity to temperature shock and oxidative stress. We further show that RNase III is important for the induction of the heat shock sigma factor RpoH and for the expression of the superoxide dismutase SodA. Full article
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15 pages, 2684 KiB  
Article
Comprehensive Transcriptomic Analysis of Heterotrophic Nitrifying Bacterium Klebsiella sp. TN-10 in Response to Nitrogen Stress
by Dan Li, Mingquan Huang, Shirong Dong, Yao Jin, Rongqing Zhou and Chongde Wu
Microorganisms 2022, 10(2), 353; https://doi.org/10.3390/microorganisms10020353 - 3 Feb 2022
Cited by 1 | Viewed by 1862
Abstract
Klebsiella sp. TN-10, a heterotrophic nitrifying bacterium, showed excellent nitrification ability under nitrogen stress. The strain was cultured under different nitrogen stress levels, including ammonium sulfate 0.5, 2.5, and 5 g/L, and samples were titled group-L, group-M, and group-H, respectively. In these three [...] Read more.
Klebsiella sp. TN-10, a heterotrophic nitrifying bacterium, showed excellent nitrification ability under nitrogen stress. The strain was cultured under different nitrogen stress levels, including ammonium sulfate 0.5, 2.5, and 5 g/L, and samples were titled group-L, group-M, and group-H, respectively. In these three groups, the removed total nitrogen was 70.28, 118.33, and 157.18 mg/L after 12 h of cultivation, respectively. An RNA-Seq transcriptome analysis was used to describe key regulatory networks in response to nitrogen stress. The GO functional enrichment and KEGG enrichment analyses showed that differentially expressed genes (DEGs) participated in more pathways under higher nitrogen stress (group-H). Carbohydrate metabolism and amino acid metabolism were the most abundant subcategories, which meant these pathways were significantly influenced by nitrogen stress and could be related to nitrogen removal. In the nitrogen cycle, up-regulated gene2311 (narK, encodes major facilitator superfamily transporter) may accelerate the entry of nitrogen into the cells and subsequently contribute to the nitrogen utilization. In addition, the up-regulation of gene2312 (narG), gene2313 (narH), and gene2315 (narH) may accelerate denitrification pathways and facilitate nitrogen removal. The results presented in this study may play a pivotal role in understanding the regulation networks of the nitrifying bacterium TN-10 under nitrogen stress. Full article
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17 pages, 2553 KiB  
Article
Bioinformatics Investigations of Universal Stress Proteins from Mercury-Methylating Desulfovibrionaceae
by Raphael D. Isokpehi, Dominique S. McInnis, Antoinette M. Destefano, Gabrielle S. Johnson, Akimio D. Walker, Yessenia A. Hall, Baraka W. Mapp, Matilda O. Johnson and Shaneka S. Simmons
Microorganisms 2021, 9(8), 1780; https://doi.org/10.3390/microorganisms9081780 - 21 Aug 2021
Cited by 1 | Viewed by 2346
Abstract
The presence of methylmercury in aquatic environments and marine food sources is of global concern. The chemical reaction for the addition of a methyl group to inorganic mercury occurs in diverse bacterial taxonomic groups including the Gram-negative, sulfate-reducing Desulfovibrionaceae family that inhabit extreme [...] Read more.
The presence of methylmercury in aquatic environments and marine food sources is of global concern. The chemical reaction for the addition of a methyl group to inorganic mercury occurs in diverse bacterial taxonomic groups including the Gram-negative, sulfate-reducing Desulfovibrionaceae family that inhabit extreme aquatic environments. The availability of whole-genome sequence datasets for members of the Desulfovibrionaceae presents opportunities to understand the microbial mechanisms that contribute to methylmercury production in extreme aquatic environments. We have applied bioinformatics resources and developed visual analytics resources to categorize a collection of 719 putative universal stress protein (USP) sequences predicted from 93 genomes of Desulfovibrionaceae. We have focused our bioinformatics investigations on protein sequence analytics by developing interactive visualizations to categorize Desulfovibrionaceae universal stress proteins by protein domain composition and functionally important amino acids. We identified 651 Desulfovibrionaceae universal stress protein sequences, of which 488 sequences had only one USP domain and 163 had two USP domains. The 488 single USP domain sequences were further categorized into 340 sequences with ATP-binding motif and 148 sequences without ATP-binding motif. The 163 double USP domain sequences were categorized into (1) both USP domains with ATP-binding motif (3 sequences); (2) both USP domains without ATP-binding motif (138 sequences); and (3) one USP domain with ATP-binding motif (21 sequences). We developed visual analytics resources to facilitate the investigation of these categories of datasets in the presence or absence of the mercury-methylating gene pair (hgcAB). Future research could utilize these functional categories to investigate the participation of universal stress proteins in the bacterial cellular uptake of inorganic mercury and methylmercury production, especially in anaerobic aquatic environments. Full article
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25 pages, 6635 KiB  
Article
Environmental Conditions Modulate the Transcriptomic Response of Both Caulobacter crescentus Morphotypes to Cu Stress
by Laurens Maertens, Pauline Cherry, Françoise Tilquin, Rob Van Houdt and Jean-Yves Matroule
Microorganisms 2021, 9(6), 1116; https://doi.org/10.3390/microorganisms9061116 - 21 May 2021
Cited by 3 | Viewed by 2985
Abstract
Bacteria encounter elevated copper (Cu) concentrations in multiple environments, varying from mining wastes to antimicrobial applications of copper. As the role of the environment in the bacterial response to Cu ion exposure remains elusive, we used a tagRNA-seq approach to elucidate the disparate [...] Read more.
Bacteria encounter elevated copper (Cu) concentrations in multiple environments, varying from mining wastes to antimicrobial applications of copper. As the role of the environment in the bacterial response to Cu ion exposure remains elusive, we used a tagRNA-seq approach to elucidate the disparate responses of two morphotypes of Caulobacter crescentus NA1000 to moderate Cu stress in a complex rich (PYE) medium and a defined poor (M2G) medium. The transcriptome was more responsive in M2G, where we observed an extensive oxidative stress response and reconfiguration of the proteome, as well as the induction of metal resistance clusters. In PYE, little evidence was found for an oxidative stress response, but several transport systems were differentially expressed, and an increased need for histidine was apparent. These results show that the Cu stress response is strongly dependent on the cellular environment. In addition, induction of the extracytoplasmic function sigma factor SigF and its regulon was shared by the Cu stress responses in both media, and its central role was confirmed by the phenotypic screening of a sigF::Tn5 mutant. In both media, stalked cells were more responsive to Cu stress than swarmer cells, and a stronger basal expression of several cell protection systems was noted, indicating that the swarmer cell is inherently more Cu resistant. Our approach also allowed for detecting several new transcription start sites, putatively indicating small regulatory RNAs, and additional levels of Cu-responsive regulation. Full article
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14 pages, 1591 KiB  
Article
Contribution of the Locus of Heat Resistance to Growth and Survival of Escherichia coli at Alkaline pH and at Alkaline pH in the Presence of Chlorine
by Tongbo Zhu, Zhiying Wang, Lynn M. McMullen, Tracy Raivio, David J. Simpson and Michael G. Gänzle
Microorganisms 2021, 9(4), 701; https://doi.org/10.3390/microorganisms9040701 - 28 Mar 2021
Cited by 5 | Viewed by 2582
Abstract
The locus of heat resistance (LHR) confers resistance to extreme heat, chlorine and oxidative stress in Escherichia coli. This study aimed to determine the function of the LHR in maintaining bacterial cell envelope homeostasis, the regulation of the genes comprising the LHR [...] Read more.
The locus of heat resistance (LHR) confers resistance to extreme heat, chlorine and oxidative stress in Escherichia coli. This study aimed to determine the function of the LHR in maintaining bacterial cell envelope homeostasis, the regulation of the genes comprising the LHR and the contribution of the LHR to alkaline pH response. The presence of the LHR did not affect the activity of the Cpx two-component regulatory system in E. coli, which was measured to quantify cell envelope stress. The LHR did not alter E. coli MG1655 growth rate in the range of pH 6.9 to 9.2. However, RT-qPCR results indicated that the expression of the LHR was elevated at pH 8.0 when CpxR was absent. The LHR did not improve survival of E. coli MG1655 at extreme alkaline pH (pH = 11.0 to 11.2) but improved survival at pH 11.0 in the presence of chlorine. Therefore, we conclude that the LHR confers resistance to extreme alkaline pH in the presence of oxidizing agents. Resistance to alkaline pH is regulated by an endogenous mechanism, including the Cpx envelope stress response, whereas the LHR confers resistance to extreme alkaline pH only in the presence of additional stress such as chlorine. Full article
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14 pages, 2118 KiB  
Article
Adaptation of Cupriavidus metallidurans CH34 to Toxic Zinc Concentrations Involves an Uncharacterized ABC-Type Transporter
by Rob Van Houdt, Joachim Vandecraen, Natalie Leys, Pieter Monsieurs and Abram Aertsen
Microorganisms 2021, 9(2), 309; https://doi.org/10.3390/microorganisms9020309 - 2 Feb 2021
Cited by 5 | Viewed by 2349
Abstract
Cupriavidus metallidurans CH34 is a well-studied metal-resistant β-proteobacterium and contains a battery of genes participating in metal metabolism and resistance. Here, we generated a mutant (CH34ZnR) adapted to high zinc concentrations in order to study how CH34 could adaptively further increase [...] Read more.
Cupriavidus metallidurans CH34 is a well-studied metal-resistant β-proteobacterium and contains a battery of genes participating in metal metabolism and resistance. Here, we generated a mutant (CH34ZnR) adapted to high zinc concentrations in order to study how CH34 could adaptively further increase its resistance against this metal. Characterization of CH34ZnR revealed that it was also more resistant to cadmium, and that it incurred seven insertion sequence-mediated mutations. Among these, an IS1088 disruption of the glpR gene (encoding a DeoR-type transcriptional repressor) resulted in the constitutive expression of the neighboring ATP-binding cassette (ABC)-type transporter. GlpR and the adjacent ABC transporter are highly similar to the glycerol operon regulator and ATP-driven glycerol importer of Rhizobium leguminosarum bv. viciae VF39, respectively. Deletion of glpR or the ABC transporter and complementation of CH34ZnR with the parental glpR gene further demonstrated that loss of GlpR function and concomitant derepression of the adjacent ABC transporter is pivotal for the observed resistance phenotype. Importantly, addition of glycerol, presumably by glycerol-mediated attenuation of GlpR activity, also promoted increased zinc and cadmium resistance in the parental CH34 strain. Upregulation of this ABC-type transporter is therefore proposed as a new adaptation route towards metal resistance. Full article
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23 pages, 3321 KiB  
Article
Comparative Analysis of the Global Transcriptomic Response to Oxidative Stress of Bacillus anthracis htrA-Disrupted and Parental Wild Type Strains
by Galia Zaide, Uri Elia, Inbar Cohen-Gihon, Ma’ayan Israeli, Shahar Rotem, Ofir Israeli, Sharon Ehrlich, Hila Cohen, Shirley Lazar, Adi Beth-Din, Avigdor Shafferman, Anat Zvi, Ofer Cohen and Theodor Chitlaru
Microorganisms 2020, 8(12), 1896; https://doi.org/10.3390/microorganisms8121896 - 30 Nov 2020
Cited by 4 | Viewed by 2393
Abstract
We previously demonstrated that the HtrA (High Temperature Requirement A) protease/chaperone active in the quality control of protein synthesis, represents an important virulence determinant of Bacillus anthracis. Virulence attenuation of htrA-disrupted Bacillus anthracis strains was attributed to susceptibility of ΔhtrA [...] Read more.
We previously demonstrated that the HtrA (High Temperature Requirement A) protease/chaperone active in the quality control of protein synthesis, represents an important virulence determinant of Bacillus anthracis. Virulence attenuation of htrA-disrupted Bacillus anthracis strains was attributed to susceptibility of ΔhtrA strains to stress insults, as evidenced by affected growth under various stress conditions. Here, we report a comparative RNA-seq transcriptomic study generating a database of differentially expressed genes in the B. anthracis htrA-disrupted and wild type parental strains under oxidative stress. The study demonstrates that, apart from protease and chaperone activities, HtrA exerts a regulatory role influencing expression of more than 1000 genes under stress. Functional analysis of groups or individual genes exhibiting strain-specific modulation, evidenced (i) massive downregulation in the ΔhtrA and upregulation in the WT strains of various transcriptional regulators, (ii) downregulation of translation processes in the WT strain, and (iii) downregulation of metal ion binding functions and upregulation of sporulation-associated functions in the ΔhtrA strain. These modulated functions are extensively discussed. Fifteen genes uniquely upregulated in the wild type strain were further interrogated for their modulation in response to other stress regimens. Overexpression of one of these genes, encoding for MazG (a nucleoside triphosphate pyrophosphohydrolase involved in various stress responses in other bacteria), in the ΔhtrA strain resulted in partial alleviation of the H2O2-sensitive phenotype. Full article
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18 pages, 3684 KiB  
Article
Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection
by Quentin Perraud, Paola Cantero, Mathilde Munier, Françoise Hoegy, Nicolas Zill, Véronique Gasser, Gaëtan L. A. Mislin, Laurence Ehret-Sabatier and Isabelle J. Schalk
Microorganisms 2020, 8(11), 1820; https://doi.org/10.3390/microorganisms8111820 - 18 Nov 2020
Cited by 21 | Viewed by 3067
Abstract
Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake process. P. [...] Read more.
Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake process. P. aeruginosa produces two siderophores and is also able to use many siderophores produced by other bacteria. We investigated the phenotypic plasticity of iron-uptake pathway expression in an epithelial cell infection assay in the presence of two different siderophore–antibiotic conjugates, one with a hydroxamate siderophore and the second with a tris-catechol. Proteomic and RT-qPCR approaches showed that P. aeruginosa was able to sense the presence of both compounds in its environment and adapt the expression of its iron uptake pathways to access iron via them. Moreover, the catechol-type siderophore–antibiotic was clearly more efficient in inducing the expression of its corresponding transporter than the hydroxamate compound when both were simultaneously present. In parallel, the expression of the proteins of the two iron uptake pathways using siderophores produced by P. aeruginosa was significantly repressed in the presence of both conjugates. Altogether, the data indicate that catechol-type siderophores are more promising vectors for antibiotic vectorization using a Trojan-horse strategy. Full article
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20 pages, 3375 KiB  
Article
Activation of the Cell Wall Stress Response in Pseudomonas aeruginosa Infected by a Pf4 Phage Variant
by Damien Tortuel, Ali Tahrioui, Sophie Rodrigues, Mélyssa Cambronel, Amine M. Boukerb, Olivier Maillot, Julien Verdon, Emile Bere, Michael Nusser, Gerald Brenner-Weiss, Audrey David, Onyedikachi Cecil Azuama, Marc G. J. Feuilloley, Nicole Orange, Olivier Lesouhaitier, Pierre Cornelis, Sylvie Chevalier and Emeline Bouffartigues
Microorganisms 2020, 8(11), 1700; https://doi.org/10.3390/microorganisms8111700 - 30 Oct 2020
Cited by 12 | Viewed by 3416
Abstract
Pseudomonas aeruginosa PAO1 has an integrated Pf4 prophage in its genome, encoding a relatively well-characterized filamentous phage, which contributes to the bacterial biofilm organization and maturation. Pf4 variants are considered as superinfectives when they can re-infect and kill the prophage-carrying host. Herein, the [...] Read more.
Pseudomonas aeruginosa PAO1 has an integrated Pf4 prophage in its genome, encoding a relatively well-characterized filamentous phage, which contributes to the bacterial biofilm organization and maturation. Pf4 variants are considered as superinfectives when they can re-infect and kill the prophage-carrying host. Herein, the response of P. aeruginosa H103 to Pf4 variant infection was investigated. This phage variant caused partial lysis of the bacterial population and modulated H103 physiology. We show by confocal laser scanning microscopy that a Pf4 variant-infection altered P. aeruginosa H103 biofilm architecture either in static or dynamic conditions. Interestingly, in the latter condition, numerous cells displayed a filamentous morphology, suggesting a link between this phenotype and flow-related forces. In addition, Pf4 variant-infection resulted in cell envelope stress response, mostly mediated by the AlgU and SigX extracytoplasmic function sigma factors (ECFσ). AlgU and SigX involvement may account, at least partly, for the enhanced expression level of genes involved in the biosynthesis pathways of two matrix exopolysaccharides (Pel and alginates) and bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) metabolism. Full article
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15 pages, 2549 KiB  
Article
In vitro Edwardsiella piscicida CK108 Transcriptome Profiles with Subinhibitory Concentrations of Phenol and Formalin Reveal New Insights into Bacterial Pathogenesis Mechanisms
by Ju Bin Yoon, Sungmin Hwang, Se-Won Baek, Seungki Lee, Woo Young Bang and Ki Hwan Moon
Microorganisms 2020, 8(7), 1068; https://doi.org/10.3390/microorganisms8071068 - 17 Jul 2020
Cited by 13 | Viewed by 3659
Abstract
Phenol and formalin are major water pollutants that are frequently discharged into the aquatic milieu. These chemicals can affect broad domains of life, including microorganisms. Aquatic pollutants, unlike terrestrial pollutants, are easily diluted in water environments and exist at a sub-inhibitory concentration (sub-IC), [...] Read more.
Phenol and formalin are major water pollutants that are frequently discharged into the aquatic milieu. These chemicals can affect broad domains of life, including microorganisms. Aquatic pollutants, unlike terrestrial pollutants, are easily diluted in water environments and exist at a sub-inhibitory concentration (sub-IC), thus not directly inhibiting bacterial growth. However, they can modulate gene expression profiles. The sub-IC values of phenol and formalin were measured by minimal inhibitory concentration (MIC) assay to be 0.146% (1.3 mM) and 0.0039% (0.38 mM), respectively, in Edwardsiella piscicida CK108, a Gram-negative fish pathogen. We investigated the differentially expressed genes (DEG) by RNA-seq when the cells were exposed to the sub-ICs of phenol and formalin. DEG analyses revealed that genes involved in major virulence factors (type I fimbriae, flagella, type III and type VI secretion system) and various cellular pathways (energy production, amino acid synthesis, carbohydrate metabolism and two-component regulatory systems) were up- or downregulated by both chemicals. The genome-wide gene expression data corresponded to the results of a quantitative reverse complementary-PCR and motility assay. This study not only provides insight into how a representative fish pathogen, E. piscicida CK108, responds to the sub-ICs of phenol and formalin but also shows the importance of controlling chemical pollutants in aquatic environments. Full article
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Review

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26 pages, 2512 KiB  
Review
Surviving Reactive Chlorine Stress: Responses of Gram-Negative Bacteria to Hypochlorous Acid
by Waleska Stephanie da Cruz Nizer, Vasily Inkovskiy and Joerg Overhage
Microorganisms 2020, 8(8), 1220; https://doi.org/10.3390/microorganisms8081220 - 11 Aug 2020
Cited by 76 | Viewed by 16674
Abstract
Sodium hypochlorite (NaOCl) and its active ingredient, hypochlorous acid (HOCl), are the most commonly used chlorine-based disinfectants. HOCl is a fast-acting and potent antimicrobial agent that interacts with several biomolecules, such as sulfur-containing amino acids, lipids, nucleic acids, and membrane components, causing severe [...] Read more.
Sodium hypochlorite (NaOCl) and its active ingredient, hypochlorous acid (HOCl), are the most commonly used chlorine-based disinfectants. HOCl is a fast-acting and potent antimicrobial agent that interacts with several biomolecules, such as sulfur-containing amino acids, lipids, nucleic acids, and membrane components, causing severe cellular damage. It is also produced by the immune system as a first-line of defense against invading pathogens. In this review, we summarize the adaptive responses of Gram-negative bacteria to HOCl-induced stress and highlight the role of chaperone holdases (Hsp33, RidA, Cnox, and polyP) as an immediate response to HOCl stress. We also describe the three identified transcriptional regulators (HypT, RclR, and NemR) that specifically respond to HOCl. Besides the activation of chaperones and transcriptional regulators, the formation of biofilms has been described as an important adaptive response to several stressors, including HOCl. Although the knowledge on the molecular mechanisms involved in HOCl biofilm stimulation is limited, studies have shown that HOCl induces the formation of biofilms by causing conformational changes in membrane properties, overproducing the extracellular polymeric substance (EPS) matrix, and increasing the intracellular concentration of cyclic-di-GMP. In addition, acquisition and expression of antibiotic resistance genes, secretion of virulence factors and induction of the viable but nonculturable (VBNC) state has also been described as an adaptive response to HOCl. In general, the knowledge of how bacteria respond to HOCl stress has increased over time; however, the molecular mechanisms involved in this stress response is still in its infancy. A better understanding of these mechanisms could help understand host-pathogen interactions and target specific genes and molecules to control bacterial spread and colonization. Full article
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