Listeria monocytogenes σB Has a Small Core Regulon and a Conserved Role in Virulence but Makes Differential Contributions to Stress Tolerance across a Diverse Collection of Strains

ABSTRACT Listeria monocytogenes strains are classified in at least three distinct phylogenetic lineages. There are correlations between lineage classification and source of bacterial isolation; e.g., human clinical and food isolates usually are classified in either lineage I or II. However, human clinical isolates are overrepresented in lineage I, while food isolates are overrepresented in lineage II. σB, a transcriptional regulator previously demonstrated to contribute to environmental stress responses and virulence in L. monocytogenes lineage II strains, was hypothesized to provide differential abilities for L. monocytogenes survival in various niches (e.g., food and human clinical niches). To determine if the contributions of σB to stress response and virulence differ across diverse L. monocytogenes strains, ΔsigB mutations were created in strains belonging to lineages I, II, IIIA, and IIIB. Paired parent and ΔsigB mutant strains were tested for survival under acid and oxidative stress conditions, Caco-2 cell invasion efficiency, and virulence using the guinea pig listeriosis infection model. Parent and ΔsigB mutant strain transcriptomes were compared using whole-genome expression microarrays. σB contributed to virulence in each strain. However, while σB contributed significantly to survival under acid and oxidative stress conditions and Caco-2 cell invasion in lineage I, II, and IIIB strains, the contributions of σB were not significant for these phenotypes in the lineage IIIA strain. A core set of 63 genes was positively regulated by σB in all four strains; different total numbers of genes were positively regulated by σB in the strains. Our results suggest that σB universally contributes to L. monocytogenes virulence but specific σB-regulated stress response phenotypes vary among strains.

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Stress Survival Islet 2, Predominantly Present in Listeria monocytogenes Strains of Sequence Type 121, Is Involved in the Alkaline and Oxidative Stress Responses

Applied and Environmental Microbiology ◽

10.1128/aem.00827-17 ◽

2017 ◽

Vol 83 (16) ◽

Cited By ~ 34

Author(s):

Eva Harter ◽

Eva Maria Wagner ◽

Andreas Zaiser ◽

Sabrina Halecker ◽

Martin Wagner ◽

...

Keyword(s):

Oxidative Stress ◽

Listeria Monocytogenes ◽

Stress Responses ◽

Food Processing ◽

Stress Conditions ◽

Content Type ◽

Oxidative Stresses ◽

Stress Survival ◽

Oxidative Stress Responses ◽

And Oxidative Stress

ABSTRACT The foodborne pathogen Listeria monocytogenes is able to survive a variety of stress conditions leading to the colonization of different niches like the food processing environment. This study focuses on the hypervariable genetic hot spot lmo0443 to lmo0449 haboring three inserts: the stress survival islet 1 (SSI-1), the single-gene insert LMOf2365_0481, and two homologous genes of the nonpathogenic species Listeria innocua: lin0464, coding for a putative transcriptional regulator, and lin0465, encoding an intracellular PfpI protease. Our prevalence study revealed a different distribution of the inserts between human and food-associated isolates. The lin0464-lin0465 insert was predominantly found in food-associated strains of sequence type 121 (ST121). Functional characterization of this insert showed that the putative PfpI protease Lin0465 is involved in alkaline and oxidative stress responses but not in acidic, gastric, heat, cold, osmotic, and antibiotic stresses. In parallel, deletion of lin0464 decreased survival under alkaline and oxidative stresses. The expression of both genes increased significantly under oxidative stress conditions independently of the alternative sigma factor σB. Furthermore, we showed that the expression of the protease gene lin0465 is regulated by the transcription factor lin0464 under stress conditions, suggesting that lin0464 and lin0465 form a functional unit. In conclusion, we identified a novel stress survival islet 2 (SSI-2), predominantly present in L. monocytogenes ST121 strains, beneficial for survival under alkaline and oxidative stresses, potentially supporting adaptation and persistence of L. monocytogenes in food processing environments. IMPORTANCE Listeria monocytogenes strains of ST121 are known to persist for months and even years in food processing environments, thereby increasing the risk of food contamination and listeriosis. However, the molecular mechanism underlying this remarkable niche-specific adaptation is still unknown. Here, we demonstrate that the genomic islet SSI-2, predominantly present in L. monocytogenes ST121 strains, is beneficial for survival under alkaline and oxidative stress conditions, which are routinely encountered in food processing environments. Our findings suggest that SSI-2 is part of a diverse set of molecular determinants contributing to niche-specific adaptation and persistence of L. monocytogenes ST121 strains in food processing environments.

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Comparison of the Stress Response of Listeria monocytogenes Strains with Sprout Colonization

Journal of Food Protection ◽

10.4315/0362-028x-71.8.1556 ◽

2008 ◽

Vol 71 (8) ◽

pp. 1556-1562 ◽

Cited By ~ 6

Author(s):

LISA GORSKI ◽

DENISE FLAHERTY ◽

JESSICA M. DUHÉ

Keyword(s):

Oxidative Stress ◽

Statistical Analysis ◽

Listeria Monocytogenes ◽

Stress Response ◽

Foodborne Pathogen ◽

Acid Stress ◽

Broccoli Sprouts ◽

Alfalfa Sprouts ◽

Different Strains ◽

And Oxidative Stress

Twenty-nine strains of the foodborne pathogen Listeria monocytogenes were tested for their ability to colonize alfalfa, radish, and broccoli sprouts and their capacity to withstand acid and oxidative stress, two stresses common to the sprouting environment. Wide variation in the ability of different strains to colonize alfalfa sprouts were confirmed, but the variations among radish and broccoli sprouts were not as large. With a few exceptions, strains that were poor colonizers of alfalfa tended to be among the poorer colonizers of radish and broccoli and vice versa. The strains also were variable in their resistance to both acid and oxidative stress. Statistical analysis revealed no correlation between acid stress and sprout colonization, but there was a positive correlation between resistance to oxidative stress and colonization of all three sprout types. Although the response to oxidative stress is important for L. monocytogenes virulence, it also may be important for life outside of a host.

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Stringent Response Governs the Virulence and Oxidative Stress Resistance of Francisella tularensis

10.1101/653790 ◽

2019 ◽

Author(s):

Zhuo Ma ◽

Kayla King ◽

Maha Alqahtani ◽

Madeline Worden ◽

Parthasarthy Muthuraman ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Francisella Tularensis ◽

Stress Resistance ◽

Stringent Response ◽

Oxidative Stress Response ◽

Stress Conditions ◽

Gram Negative ◽

And Oxidative Stress ◽

Starvation Conditions

AbstractFrancisella tularensis is a Gram-negative bacterium responsible for causing tularemia in the northern hemisphere. F. tularensis has long been developed as a biological weapon due to its ability to cause severe illness upon inhalation of as few as ten organisms and based on its potential to be used as a bioterror agent is now classified as a Tier 1 Category A select agent by the CDC. The stringent response facilitates bacterial survival under nutritionally challenging starvation conditions. The hallmark of stringent response is the accumulation of the effector molecules ppGpp and (p)ppGpp known as stress alarmones. The relA and spoT gene products generate alarmones in several Gram-negative bacterial pathogens. RelA is a ribosome-associated ppGpp synthetase that gets activated under amino acid starvation conditions whereas, SpoT is a bifunctional enzyme with both ppGpp synthetase and ppGpp hydrolase activities. Francisella encodes a monofunctional RelA and a bifunctional SpoT enzyme. Previous studies have demonstrated that stringent response under nutritional stresses increases expression of virulence-associated genes encoded on Francisella Pathogenicity Island. This study investigated how stringent response governs the oxidative stress response of F. tularensis. We demonstrate that RelA/SpoT-mediated ppGpp production alters global gene transcriptional profile of F. tularensis in the presence of oxidative stress. The lack of stringent response in relA/spoT gene deletion mutants of F. tularensis makes bacteria more susceptible to oxidants, attenuates survival in macrophages, and virulence in mice. Mechanistically, we provide evidence that the stringent response in Francisella contributes to oxidative stress resistance by enhancing the production of antioxidant enzymes.ImportanceThe unique intracellular life cycle of Francisella in addition to nutritional stress also exposes the bacteria to oxidative stress conditions upon its brief residence in the phagosomes, and escape into the cytosol where replication takes place. However, the contribution of the stringent response in gene regulation and management of the oxidative stress response when Francisella is experiencing oxidative stress conditions is not known. Our results provide a link between the stringent and oxidative stress responses. This study further improves our understanding of the intracellular survival mechanisms of F. tularensis.

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Repressive effect of Rhus coriaria L. fruit extracts on microglial cells-mediated inflammatory and oxidative stress responses

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.113748 ◽

2021 ◽

Vol 269 ◽

pp. 113748

Author(s):

Mohamad Khalil ◽

Ali Bazzi ◽

Dana Zeineddine ◽

Wissam Jomaa ◽

Ahmad Daher ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Responses ◽

Microglial Cells ◽

Fruit Extracts ◽

Repressive Effect ◽

Rhus Coriaria ◽

Oxidative Stress Responses ◽

And Oxidative Stress

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Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03756-3 ◽

2021 ◽

Author(s):

Sinan Xiong ◽

Wee-Joo Chng ◽

Jianbiao Zhou

Keyword(s):

Oxidative Stress ◽

Multiple Myeloma ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Cell Fate ◽

Stress Responses ◽

Plasma Cells ◽

Reactive Oxygen Species Generation ◽

Future Research ◽

And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

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Environmental Conditions Modulate the Transcriptomic Response of Both Caulobacter crescentus Morphotypes to Cu Stress

Microorganisms ◽

10.3390/microorganisms9061116 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1116

Author(s):

Laurens Maertens ◽

Pauline Cherry ◽

Françoise Tilquin ◽

Rob Van Houdt ◽

Jean-Yves Matroule

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Stress Responses ◽

Caulobacter Crescentus ◽

Oxidative Stress Response ◽

Transport Systems ◽

Transcriptomic Response ◽

Swarmer Cell ◽

Cu Stress ◽

Cellular Environment

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.

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Clade III cytokinin response factors share common roles in response to oxidative stress responses linked to cytokinin synthesis

Journal of Experimental Botany ◽

10.1093/jxb/erab076 ◽

2021 ◽

Vol 72 (8) ◽

pp. 3294-3306

Author(s):

Ariel M Hughes ◽

H Tucker Hallmark ◽

Lenka Plačková ◽

Ondrej Novák ◽

Aaron M Rashotte

Keyword(s):

Oxidative Stress ◽

Transcription Factors ◽

Stress Response ◽

Stress Responses ◽

Oxidative Stress Response ◽

Response Factors ◽

Ontology Term ◽

Regulated Expression ◽

Cytokinin Response ◽

Oxidative Stress Responses

Abstract Cytokinin response factors (CRFs) are transcription factors that are involved in cytokinin (CK) response, as well as being linked to abiotic stress tolerance. In particular, oxidative stress responses are activated by Clade III CRF members, such as AtCRF6. Here we explored the relationships between Clade III CRFs and oxidative stress. Transcriptomic responses to oxidative stress were determined in two Clade III transcription factors, Arabidopsis AtCRF5 and tomato SlCRF5. AtCRF5 was required for regulated expression of >240 genes that are involved in oxidative stress response. Similarly, SlCRF5 was involved in the regulated expression of nearly 420 oxidative stress response genes. Similarities in gene regulation by these Clade III members in response to oxidative stress were observed between Arabidopsis and tomato, as indicated by Gene Ontology term enrichment. CK levels were also changed in response to oxidative stress in both species. These changes were regulated by Clade III CRFs. Taken together, these findings suggest that Clade III CRFs play a role in oxidative stress response as well as having roles in CK signaling.

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