Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics

ABSTRACT Infection of the human stomach caused by Helicobacter pylori is very common, as the pathogen colonizes more than half of the world’s population. It is associated with varied outcomes of infection, such as peptic ulcer disease, gastric ulcers, and mucosa-associated lymphoid tissue lymphoma,...

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Autores principales:	Majjid A. Qaria, Naveen Kumar, Arif Hussain, Shamsul Qumar, Sankara N. Doddam, Ludovico P. Sepe, Niyaz Ahmed
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	H. pylori cholesteryl glucosides morphology membrane permeability antibiotic susceptibility biofilm formation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/69b520a3caa44324a0e6d67a86a04fea
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spelling	oai:doaj.org-article:69b520a3caa44324a0e6d67a86a04fea2021-11-15T15:52:18ZRoles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics10.1128/mBio.01523-182150-7511https://doaj.org/article/69b520a3caa44324a0e6d67a86a04fea2018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01523-18https://doaj.org/toc/2150-7511ABSTRACT Infection of the human stomach caused by Helicobacter pylori is very common, as the pathogen colonizes more than half of the world’s population. It is associated with varied outcomes of infection, such as peptic ulcer disease, gastric ulcers, and mucosa-associated lymphoid tissue lymphoma, and is generally considered a risk factor for the development of gastric adenocarcinoma. Cholesteryl glucosides (CGs) constitute a vital component of the cell wall of H. pylori and contribute to its pathogenicity and virulence. The hp0421 gene, which encodes cholesteryl-α-glucoside transferase (CGT), appears critical for the enzymatic function of integrating unique CGs into the cell wall of H. pylori, and deletion of this gene leads to depletion of CGs and their variants. Herein, we report that the deletion of hp0421 and consequent deficiency of cholesterol alter the morphology, shape, and cell wall composition of H. pylori cells, as demonstrated by high-resolution confocal microscopy and flow cytometry analyses of two different type strains of H. pylori, their isogenic knockouts as well as a reconstituted strain. Moreover, measurement of ethidium bromide (EtBr) influx by flow cytometry showed that lack of CGs increased cell wall permeability. Antimicrobial susceptibility testing revealed that the hp0421 isogenic knockout strains (Hp26695Δ421 and Hp76Δ421) were sensitive to antibiotics, such as fosfomycin, polymyxin B, colistin, tetracycline, and ciprofloxacin, in contrast to the wild-type strains that were resistant to the above antibiotics and tended to form denser biofilms. Lipid profile analysis of both Hp76 and Hp76Δ421 strains showed an aberrant profile of lipopolysaccharides (LPS) in the Hp76Δ421 strain. Taken together, we herein provide a set of mechanistic evidences to demonstrate that CGs play critical roles in the maintenance of the typical spiral morphology of H. pylori and its cell wall integrity, and any alteration in CG content affects the characteristic morphological features and renders the H. pylori susceptible to various antibiotics. IMPORTANCE Helicobacter pylori is an important cause of chronic gastritis leading to peptic ulcer and is a major risk factor for gastric malignancies. Failure in the eradication of H. pylori infection and increasing antibiotic resistance are two major problems in preventing H. pylori colonization. Hence, a deeper understanding of the bacterial survival strategies is needed to tackle the increasing burden of H. pylori infection by an appropriate intervention. Our study demonstrated that the lack of cholesteryl glucosides (CGs) remarkably altered the morphology of H. pylori and increased permeability of the bacterial cell wall. Further, this study highlighted the substantial role of CGs in maintaining the typical H. pylori morphology that is essential for retaining its pathogenic potential. We also demonstrated that the loss of CGs in H. pylori renders the bacterium susceptible to different antibiotics.Majjid A. QariaNaveen KumarArif HussainShamsul QumarSankara N. DoddamLudovico P. SepeNiyaz AhmedAmerican Society for MicrobiologyarticleH. pyloricholesteryl glucosidesmorphologymembrane permeabilityantibiotic susceptibilitybiofilm formationMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	H. pylori cholesteryl glucosides morphology membrane permeability antibiotic susceptibility biofilm formation Microbiology QR1-502
spellingShingle	H. pylori cholesteryl glucosides morphology membrane permeability antibiotic susceptibility biofilm formation Microbiology QR1-502 Majjid A. Qaria Naveen Kumar Arif Hussain Shamsul Qumar Sankara N. Doddam Ludovico P. Sepe Niyaz Ahmed Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics
description	ABSTRACT Infection of the human stomach caused by Helicobacter pylori is very common, as the pathogen colonizes more than half of the world’s population. It is associated with varied outcomes of infection, such as peptic ulcer disease, gastric ulcers, and mucosa-associated lymphoid tissue lymphoma, and is generally considered a risk factor for the development of gastric adenocarcinoma. Cholesteryl glucosides (CGs) constitute a vital component of the cell wall of H. pylori and contribute to its pathogenicity and virulence. The hp0421 gene, which encodes cholesteryl-α-glucoside transferase (CGT), appears critical for the enzymatic function of integrating unique CGs into the cell wall of H. pylori, and deletion of this gene leads to depletion of CGs and their variants. Herein, we report that the deletion of hp0421 and consequent deficiency of cholesterol alter the morphology, shape, and cell wall composition of H. pylori cells, as demonstrated by high-resolution confocal microscopy and flow cytometry analyses of two different type strains of H. pylori, their isogenic knockouts as well as a reconstituted strain. Moreover, measurement of ethidium bromide (EtBr) influx by flow cytometry showed that lack of CGs increased cell wall permeability. Antimicrobial susceptibility testing revealed that the hp0421 isogenic knockout strains (Hp26695Δ421 and Hp76Δ421) were sensitive to antibiotics, such as fosfomycin, polymyxin B, colistin, tetracycline, and ciprofloxacin, in contrast to the wild-type strains that were resistant to the above antibiotics and tended to form denser biofilms. Lipid profile analysis of both Hp76 and Hp76Δ421 strains showed an aberrant profile of lipopolysaccharides (LPS) in the Hp76Δ421 strain. Taken together, we herein provide a set of mechanistic evidences to demonstrate that CGs play critical roles in the maintenance of the typical spiral morphology of H. pylori and its cell wall integrity, and any alteration in CG content affects the characteristic morphological features and renders the H. pylori susceptible to various antibiotics. IMPORTANCE Helicobacter pylori is an important cause of chronic gastritis leading to peptic ulcer and is a major risk factor for gastric malignancies. Failure in the eradication of H. pylori infection and increasing antibiotic resistance are two major problems in preventing H. pylori colonization. Hence, a deeper understanding of the bacterial survival strategies is needed to tackle the increasing burden of H. pylori infection by an appropriate intervention. Our study demonstrated that the lack of cholesteryl glucosides (CGs) remarkably altered the morphology of H. pylori and increased permeability of the bacterial cell wall. Further, this study highlighted the substantial role of CGs in maintaining the typical H. pylori morphology that is essential for retaining its pathogenic potential. We also demonstrated that the loss of CGs in H. pylori renders the bacterium susceptible to different antibiotics.
format	article
author	Majjid A. Qaria Naveen Kumar Arif Hussain Shamsul Qumar Sankara N. Doddam Ludovico P. Sepe Niyaz Ahmed
author_facet	Majjid A. Qaria Naveen Kumar Arif Hussain Shamsul Qumar Sankara N. Doddam Ludovico P. Sepe Niyaz Ahmed
author_sort	Majjid A. Qaria
title	Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics
title_short	Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics
title_full	Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics
title_fullStr	Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics
title_full_unstemmed	Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics
title_sort	roles of cholesteryl-α-glucoside transferase and cholesteryl glucosides in maintenance of <named-content content-type="genus-species">helicobacter pylori</named-content> morphology, cell wall integrity, and resistance to antibiotics
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/69b520a3caa44324a0e6d67a86a04fea
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Roles of Cholesteryl-α-Glucoside Transferase and Cholesteryl Glucosides in Maintenance of <named-content content-type="genus-species">Helicobacter pylori</named-content> Morphology, Cell Wall Integrity, and Resistance to Antibiotics

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