Characterization of two bacterial proteins (ArlA and ArlB) associated with resistance to host defense peptides

10.32920/ryerson.14662941 ◽

2021 ◽

Author(s):

Mario Antonio Vargas

Keyword(s):

Host Defense ◽

Pathogenic Bacteria ◽

Genetic Locus ◽

Core Gene ◽

Two Component System ◽

Host Defense Peptides ◽

New Genes ◽

Inflammatory Bowel ◽

Defense Peptides ◽

High Level

Inflammatory bowel disease is a complex condition with a multifactorial etiology. An interplay of various factors can lead to an inflamed gut with the overproduction of host-defense peptides (HDPs) and microbiome alterations, such as increases in pathogenic bacteria. Through processes involving either core gene regulation or acquisition of new genes, bacteria have evolved mechanisms to resist HDPs. Previously, a novel genetic locus, arlABC, was identified in adherent-invasive Escherichia coli (AIEC) strain NRG857c that contributes to high-level HDP resistance. ArlC is an outer membrane protease, but the function(s) of ArlA and ArlB are unknown. Thus, characterization was performed on strains mutated in these genes. Lipopolysaccharide gels suggest a change in the core structure of the mutant strains, but several phenotypic assays gave varying results. We demonstrate that the ArlB protein is regulated by the PhoPQ two-component system. We anticipate that these investigations will lead to a better understanding of HDP resistance in AIEC.

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Heterogeneity In Two-Component Signaling Systems Within Different Strains Of Inflammatory Bowel Disease Associated Escherichia Coli.

10.32920/ryerson.14648706 ◽

2021 ◽

Author(s):

Adam Khan

Keyword(s):

Escherichia Coli ◽

Inflammatory Bowel Disease ◽

Host Defense ◽

Bowel Disease ◽

Critical Feature ◽

Host Defense Peptides ◽

Two Component ◽

Inflammatory Bowel ◽

Defense Peptides ◽

Different Strains

Resistance to host-defense peptides is a critical feature of many pathogens. Previous work in the McPhee lab has demonstrated that different strains of inflammatory bowel disease-associated Escherichia coli exhibit diverse resistance to host defense peptides. The PhoPQ two-component system is a well-characterized signaling pathway that regulates the expression of genes involved in resistance to these peptides. We hypothesize that strains have an altered capacity to signal through this system, resulting in different resistance profiles. We created a promoter-GFP fusion of two PhoPQ regulated genes, pmrD and ompT, to monitor PhoPQ signaling in eight clinical isolates. Our data shows that strains have robust differences in signaling when cultured identical conditions, supporting our hypothesis. Further, our signaling match polymyxin B resistance when using the same isolates and conditions. Our data strongly suggests that strains have an altered potential to respond to environmental signals, ultimately resulting in a broad level of resistance phenotypes.

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Heterogeneity In Two-Component Signaling Systems Within Different Strains Of Inflammatory Bowel Disease Associated Escherichia Coli.

10.32920/ryerson.14648706.v1 ◽

2021 ◽

Author(s):

Adam Khan

Keyword(s):

Escherichia Coli ◽

Inflammatory Bowel Disease ◽

Host Defense ◽

Bowel Disease ◽

Critical Feature ◽

Host Defense Peptides ◽

Two Component ◽

Inflammatory Bowel ◽

Defense Peptides ◽

Different Strains

Resistance to host-defense peptides is a critical feature of many pathogens. Previous work in the McPhee lab has demonstrated that different strains of inflammatory bowel disease-associated Escherichia coli exhibit diverse resistance to host defense peptides. The PhoPQ two-component system is a well-characterized signaling pathway that regulates the expression of genes involved in resistance to these peptides. We hypothesize that strains have an altered capacity to signal through this system, resulting in different resistance profiles. We created a promoter-GFP fusion of two PhoPQ regulated genes, pmrD and ompT, to monitor PhoPQ signaling in eight clinical isolates. Our data shows that strains have robust differences in signaling when cultured identical conditions, supporting our hypothesis. Further, our signaling match polymyxin B resistance when using the same isolates and conditions. Our data strongly suggests that strains have an altered potential to respond to environmental signals, ultimately resulting in a broad level of resistance phenotypes.

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Host Defense Peptide Resistance Contributes to Colonization and Maximal Intestinal Pathology by Crohn's Disease-Associated Adherent-Invasive Escherichia coli

Infection and Immunity ◽

10.1128/iai.01888-14 ◽

2014 ◽

Vol 82 (8) ◽

pp. 3383-3393 ◽

Cited By ~ 25

Author(s):

Joseph B. McPhee ◽

Cherrie L. Small ◽

Sarah A. Reid-Yu ◽

John R. Brannon ◽

Hervé Le Moual ◽

...

Keyword(s):

Escherichia Coli ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Host Defense ◽

Bacterial Killing ◽

Host Defense Peptides ◽

Content Type ◽

Host Defense Peptide ◽

Defense Peptides ◽

High Level

ABSTRACTHost defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associatedEscherichia colicommonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasiveE. coli(AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6,arlA, which encodes a Mig-14 family protein implicated in defensin resistance, andarlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut.

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Geographically Distinct Expression Profile of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae

Asian Herpetological Research ◽

10.3724/sp.j.1245.2013.00288 ◽

2014 ◽

Vol 4 (4) ◽

pp. 288-297

Author(s):

LING Guiying ◽

LI Li ◽

GAO Jiuxiang ◽

YU Haining ◽

WANG Yipeng ◽

...

Keyword(s):

Host Defense ◽

Expression Profile ◽

Host Defense Peptides ◽

Defense Peptides

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Human Host Defense Peptides - Role in Maintaining Human Homeostasis and Pathological Processes

Current Medicinal Chemistry ◽

10.2174/0929867323666161213100443 ◽

2017 ◽

Vol 24 (7) ◽

pp. 654-672 ◽

Cited By ~ 2

Author(s):

Malgorzata Anna Dawgul ◽

Katarzyna E. Greber ◽

Wieslaw Sawicki ◽

Wojciech Kamysz

Keyword(s):

Host Defense ◽

Host Defense Peptides ◽

Human Host ◽

Defense Peptides

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Mechanistic Fingerprinting Reveals Kinetic Signatures of Resistance to Daptomycin and Host Defense Peptides in Streptococcus mitis-oralis

Antibiotics ◽

10.3390/antibiotics10040404 ◽

2021 ◽

Vol 10 (4) ◽

pp. 404

Author(s):

Michael R. Yeaman ◽

Liana C. Chan ◽

Nagendra N. Mishra ◽

Arnold S. Bayer

Keyword(s):

Flow Cytometry ◽

Host Defense ◽

Durable Resistance ◽

Cross Resistance ◽

Streptococcus Mitis ◽

Host Defense Peptides ◽

Strain Pair ◽

Defense Peptides

Streptococcus mitis-oralis (S. mitis-oralis) infections are increasingly prevalent in specific populations, including neutropenic cancer and endocarditis patients. S. mitis-oralis strains have a propensity to evolve rapid, high-level and durable resistance to daptomycin (DAP-R) in vitro and in vivo, although the mechanism(s) involved remain incompletely defined. We examined mechanisms of DAP-R versus cross-resistance to cationic host defense peptides (HDPs), using an isogenic S. mitis-oralis strain-pair: (i) DAP-susceptible (DAP-S) parental 351-WT (DAP MIC = 0.5 µg/mL), and its (ii) DAP-R variant 351-D10 (DAP MIC > 256 µg/mL). DAP binding was quantified by flow cytometry, in-parallel with temporal (1–4 h) killing by either DAP or comparative prototypic cationic HDPs (hNP-1; LL-37). Multicolor flow cytometry was used to determine kinetic cell responses associated with resistance or susceptibility to these molecules. While overall DAP binding was similar between strains, a significant subpopulation of 351-D10 cells hyper-accumulated DAP (>2–4-fold vs. 351-WT). Further, both DAP and hNP-1 induced cell membrane (CM) hyper-polarization in 351-WT, corresponding to significantly greater temporal DAP-killing (vs. 351-D10). No strain-specific differences in CM permeabilization, lipid turnover or regulated cell death were observed post-exposure to DAP, hNP-1 or LL-37. Thus, the adaptive energetics of the CM appear coupled to the outcomes of interactions of S. mitis-oralis with DAP and selected HDPs. In contrast, altered CM permeabilization, proposed as a major mechanism of action of both DAP and HDPs, did not differentiate DAP-S vs. DAP-R phenotypes in this S. mitis-oralis strain-pair.

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