scholarly journals Helicobacter pyloriBiofilm Formation and Its Potential Role in Pathogenesis

2018 ◽  
Vol 82 (2) ◽  
Author(s):  
Skander Hathroubi ◽  
Stephanie L. Servetas ◽  
Ian Windham ◽  
D. Scott Merrell ◽  
Karen M. Ottemann
Keyword(s):  
Extracellular Polymeric Substances ◽  
Antimicrobial Treatment ◽  
Gastric Ulcers ◽  
Chronic Infections ◽  
Content Type ◽  
Mucosal Layer ◽  
Urease Production ◽  
H Pylori ◽  
Biofilm Structure

SUMMARYDespite decades of effort,Helicobacter pyloriinfections remain difficult to treat. Over half of the world's population is infected byH. pylori, which is a major cause of duodenal and gastric ulcers as well as gastric cancer. During chronic infection,H. pylorilocalizes within the gastric mucosal layer, including deep within invaginations called glands; thanks to its impressive ability to survive despite the harsh acidic environment, it can persist for the host's lifetime. This ability to survive and persist in the stomach is associated with urease production, chemotactic motility, and the ability to adapt to the fluctuating environment. Additionally, biofilm formation has recently been suggested to play a role in colonization. Biofilms are surface-associated communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances. Biofilms pose a substantial health risk and are key contributors to many chronic and recurrent infections. This link between biofilm-associated bacteria and chronic infections likely results from an increased tolerance to conventional antibiotic treatments as well as immune system action. The role of this biofilm mode in antimicrobial treatment failure andH. pylorisurvival has yet to be determined. Furthermore, relatively little is known about theH. pyloribiofilm structure or the genes associated with this mode of growth. In this review, therefore, we aim to highlight recent findings concerningH. pyloribiofilms and the molecular mechanism of their formation. Additionally, we discuss the potential roles of biofilms in the failure of antibiotic treatment and in infection recurrence.

scholarly journals Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

2016 ◽  
Vol 84 (12) ◽  
pp. 3338-3349 ◽  
Author(s):  
Amber C. Beckett ◽  
M. Blanca Piazuelo ◽  
Jennifer M. Noto ◽  
Richard M. Peek ◽  
M. Kay Washington ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Gastric Ulceration ◽  
High Salt ◽  
Gastric Ulcers ◽  
Deficiency Anemia ◽  
Content Type ◽  
H Pylori

Epidemiologic studies have provided conflicting data regarding an association betweenHelicobacter pyloriinfection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role ofH. pyloriinfection, as well as a possible role of diet, inH. pylori-associated IDA. Mongolian gerbils (eitherH. pyloriinfected or uninfected) received a normal diet or one of three diets associated with increasedH. pylorivirulence: high-salt, low-iron, or a combination of a high-salt and low-iron diet. In an analysis of all infected animals compared to uninfected animals (independent of diet),H. pylori-infected gerbils had significantly lower hemoglobin values than their uninfected counterparts at 16 weeks postinfection (P< 0.0001). The mean corpuscular volume (MCV) and serum ferritin values were significantly lower inH. pylori-infected gerbils than in uninfected gerbils, consistent with IDA. Leukocytosis and thrombocytosis were also detected in infected gerbils, indicating the presence of a systemic inflammatory response. In comparison to uninfected gerbils,H. pylori-infected gerbils had a higher gastric pH, a higher incidence of gastric ulcers, and a higher incidence of fecal occult blood loss. Anemia was associated with the presence of gastric ulceration but not gastric cancer. Infected gerbils consuming diets with a high salt content developed gastric ulcers significantly more frequently than gerbils consuming a normal-salt diet, and the lowest hemoglobin levels were in infected gerbils consuming a high-salt/low-iron diet. These data indicate thatH. pyloriinfection can cause IDA and that the composition of the diet influences the incidence and severity ofH. pylori-induced IDA.

scholarly journals Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Adria Carbo ◽  
Danyvid Olivares-Villagómez ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera ◽  
Rupesh Chaturvedi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Wild Type ◽  
Content Type ◽  
Interleukin 21 ◽  
H Pylori ◽  
Deficient Mice

ABSTRACTThe development of gastritis duringHelicobacter pyloriinfection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa duringH. pyloriinfection, we combined mathematical modeling of CD4+T cell differentiation within vivomechanistic studies. We infected IL-21-deficient and wild-type mice withH. pyloristrain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. ChronicallyH. pylori-infected IL-21-deficient mice had higherH. pyloricolonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. Thesein vivodata were used to calibrate anH. pyloriinfection-dependent, CD4+T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-γ) and IL-17 during chronicH. pyloriinfection. The model predicted activated expression of T-bet and RORγt and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4+splenocyte-specifictbx21androrcexpression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4+T cell-specific IL-10 expression inH. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronicH. pyloriinfection in a STAT1- and STAT3-dependent manner, therefore playing a major role controllingH. pyloriinfection and gastritis.IMPORTANCEHelicobacter pyloriis the dominant member of the gastric microbiota in more than 50% of the world’s population.H. pyloricolonization has been implicated in gastritis and gastric cancer, as infection withH. pyloriis the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis duringH. pyloriinfection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized withH. pylorias an alternative to aggressive antibiotics.

scholarly journals Motility-Independent Formation of Antibiotic-TolerantPseudomonas aeruginosaAggregates

2019 ◽  
Vol 85 (14) ◽  
Author(s):  
Sally Demirdjian ◽  
Hector Sanchez ◽  
Daniel Hopkins ◽  
Brent Berwin
Keyword(s):  
Biofilm Formation ◽  
Bacterial Pathogen ◽  
Aggregate Formation ◽  
Flagellar Motility ◽  
Wild Type ◽  
Chronic Infections ◽  
Content Type ◽  
Temporal Adaptation ◽  
Bacterial Aggregates

ABSTRACTPseudomonas aeruginosais a bacterial pathogen that causes severe chronic infections in immunocompromised individuals. This bacterium is highly adaptable to its environments, which frequently select for traits that promote bacterial persistence. A clinically significant temporal adaptation is the formation of surface- or cell-adhered bacterial biofilms that are associated with increased resistance to immune and antibiotic clearance. Extensive research has shown that bacterial flagellar motility promotes formation of such biofilms, whereupon the bacteria subsequently become nonmotile. However, recent evidence shows that antibiotic-tolerant nonattached bacterial aggregates, distinct from surface-adhered biofilms, can form, and these have been reported in the context of lung infections, otitis media, nonhealing wounds, and soft tissue fillers. It is unclear whether the same bacterial traits are required for aggregate formation as for biofilm formation. In this report, using isogenic mutants, we demonstrate thatP. aeruginosaaggregates in liquid cultures are spontaneously formed independent of bacterial flagellar motility and independent of an exogenous scaffold. This contrasts with the role of the flagellum to initiate surface-adhered biofilms. Similarly to surface-attached biofilms, these aggregates exhibit increased antibiotic tolerance compared to planktonic cultures. These findings provide key insights into the requirements for aggregate formation that contrast with those for biofilm formation and that may have relevance for the persistence and dissemination of nonmotile bacteria found within chronic clinical infections.IMPORTANCEIn this work, we have investigated the role of bacterial motility with regard to antibiotic-tolerant bacterial aggregate formation. Previous work has convincingly demonstrated thatP. aeruginosaflagellar motility promotes the formation of surface-adhered biofilms in many systems. In contrast, aggregate formation byP. aeruginosawas observed for nonmotile but not for motile cells in the presence of an exogenous scaffold. Here, we demonstrate that both wild-typeP. aeruginosaand mutants that genetically lack motility spontaneously form antibiotic-tolerant aggregates in the absence of an exogenously added scaffold. Additionally, we also demonstrate that wild-type (WT) and nonmotileP. aeruginosabacteria can coaggregate, shedding light on potential physiological interactions and heterogeneity of aggregates.

scholarly journals Potential Role of Nitrite for Abiotic Fe(II) Oxidation and Cell Encrustation during Nitrate Reduction by Denitrifying Bacteria

2013 ◽  
Vol 80 (3) ◽  
pp. 1051-1061 ◽  
Author(s):  
Nicole Klueglein ◽  
Fabian Zeitvogel ◽  
York-Dieter Stierhof ◽  
Matthias Floetenmeyer ◽  
Kurt O. Konhauser ◽  
...  
Keyword(s):  
Extracellular Polymeric Substances ◽  
Potential Role ◽  
Paracoccus Denitrificans ◽  
Culture Media ◽  
Content Type ◽  
Lectin Staining ◽  
Nitrate Reducers ◽  
Close Proximity ◽  
Oxidation Mechanisms

ABSTRACTMicroorganisms have been observed to oxidize Fe(II) at neutral pH under anoxic and microoxic conditions. While most of the mixotrophic nitrate-reducing Fe(II)-oxidizing bacteria become encrusted with Fe(III)-rich minerals, photoautotrophic and microaerophilic Fe(II) oxidizers avoid cell encrustation. The Fe(II) oxidation mechanisms and the reasons for encrustation remain largely unresolved. Here we used cultivation-based methods and electron microscopy to compare two previously described nitrate-reducing Fe(II) oxidizers (Acidovoraxsp. strain BoFeN1 andPseudogulbenkianiasp. strain 2002) and two heterotrophic nitrate reducers (Paracoccus denitrificansATCC 19367 andP. denitrificansPd 1222). All four strains oxidized ∼8 mM Fe(II) within 5 days in the presence of 5 mM acetate and accumulated nitrite (maximum concentrations of 0.8 to 1.0 mM) in the culture media. Iron(III) minerals, mainly goethite, formed and precipitated extracellularly in close proximity to the cell surface. Interestingly, mineral formation was also observed within the periplasm and cytoplasm; intracellular mineralization is expected to be physiologically disadvantageous, yet acetate consumption continued to be observed even at an advanced stage of Fe(II) oxidation. Extracellular polymeric substances (EPS) were detected by lectin staining with fluorescence microscopy, particularly in the presence of Fe(II), suggesting that EPS production is a response to Fe(II) toxicity or a strategy to decrease encrustation. Based on the data presented here, we propose a nitrite-driven, indirect mechanism of cell encrustation whereby nitrite forms during heterotrophic denitrification and abiotically oxidizes Fe(II). This work adds to the known assemblage of Fe(II)-oxidizing bacteria in nature and complicates our ability to delineate microbial Fe(II) oxidation in ancient microbes preserved as fossils in the geological record.

Helicobacter pylori Biofilm and New Strategies to Combat it

2020 ◽  
Vol 20 ◽  
Author(s):  
Majid Taati Moghadam ◽  
Zahra Chegini ◽  
Amin Khoshbayan ◽  
Iman Farahani ◽  
Aref Shariati
Keyword(s):  
Helicobacter Pylori ◽  
Biofilm Formation ◽  
Extracellular Polymeric Substances ◽  
Combination Therapies ◽  
Chronic Infections ◽  
Chemical Substances ◽  
And Performance ◽  
H Pylori ◽  
Initial Binding ◽  
New Strategies

: Helicobacter pylori, the most frequent pathogens worldwide that colonize around 50% of the world’s population, cause important diseases such as gastric adenocarcinoma, chronic gastritis, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In recent years, various studies have reported that H. pylori biofilm may be one of the critical barriers to the eradication of this bacterial infection. Biofilms inhibit the penetration of antibiotics, increase the expression of efflux pumps and mutations, multiple therapeutic failures, and chronic infections. Nanoparticles and natural products can demolish H. pylori biofilm by destroying the outer layers and inhibiting the initial binding of bacteria. Also, the use of combination therapies destroying extracellular polymeric substances decreases coccoid forms of bacteria and degrading polysaccharides in the outer matrix that lead to an increase in the permeability and performance of antibiotics. Different probiotics, antimicrobial peptides, chemical substances, and polysaccharides by inhibiting adhesion and colonization of H. pylori can prevent biofilm formation by this bacterium. Of note, many of the above are applicable to acidic pH and can be used to treat gastritis. Therefore, H. pylori biofilm may be one of the major causes of failure to the eradication of infections caused by this bacterium, and antibiotics are not capable of destroying the biofilm. Thus, it is necessary to use new strategies to prevent recurrent and chronic infections by inhibiting biofilm formation.

scholarly journals Breaking the Vicious Cycle of Antibiotic Killing and Regrowth of Biofilm-ResidingPseudomonas aeruginosa

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Mathias Müsken ◽  
Vinay Pawar ◽  
Timo Schwebs ◽  
Heike Bähre ◽  
Sebastian Felgner ◽  
...  
Keyword(s):  
Treatment Success ◽  
Antimicrobial Treatment ◽  
Vicious Cycle ◽  
Chronic Infections ◽  
Treatment Protocols ◽  
Content Type ◽  
Treatment Regimens ◽  
Biofilm Bacteria ◽  
Time Required

ABSTRACTBiofilm-residing bacteria embedded in an extracellular matrix are protected from diverse physicochemical insults. In addition to the general recalcitrance of biofilm bacteria, high bacterial loads in biofilm-associated infections significantly diminish the efficacy of antimicrobials due to a low per-cell antibiotic concentration. Accordingly, present antimicrobial treatment protocols that have been established to serve the eradication of acute infections fail to clear biofilm-associated chronic infections. In the present study, we applied automated confocal microscopy onPseudomonas aeruginosato monitor dynamic killing of biofilm-grown bacteria by tobramycin and colistin in real time. We revealed that the time required for surviving bacteria to repopulate the biofilm could be taken as a measure for effectiveness of the antimicrobial treatment. It depends on the (i) nature and concentration of the antibiotic, (ii) duration of antibiotic treatment, (iii) application as monotherapy or combination therapy, and (iv) interval of drug administration. The vicious cycle of killing and repopulation of biofilm bacteria could also be broken in anin vivomodel system by applying successive antibiotic dosages at intervals that do not allow full reconstitution of the biofilm communities. Treatment regimens that consider the important aspects of antimicrobial killing kinetics bear the potential to improve control of biofilm regrowth. This is an important and underestimated factor that is bound to ensure sustainable treatment success of chronic infections.

scholarly journals Epigenetic Regulation Alters Biofilm Architecture and Composition in Multiple Clinical Isolates of Nontypeable Haemophilus influenzae

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Kenneth L. Brockman ◽  
Patrick N. Azzari ◽  
M. Taylor Branstool ◽  
John M. Atack ◽  
Benjamin L. Schulz ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Biofilm Formation ◽  
Human Pathogens ◽  
Content Type ◽  
Alkaline Conditions ◽  
Tract Infections ◽  
Biofilm Structure

ABSTRACT Biofilms play a critical role in the colonization, persistence, and pathogenesis of many human pathogens. Multiple mucosa-associated pathogens have evolved a mechanism of rapid adaptation, termed the phasevarion, which facilitates a coordinated regulation of numerous genes throughout the bacterial genome. This epigenetic regulation occurs via phase variation of a DNA methyltransferase, Mod. The phasevarion of nontypeable Haemophilus influenzae (NTHI) significantly affects the severity of experimental otitis media and regulates several disease-related processes. However, the role of the NTHI phasevarion in biofilm formation is unclear. The present study shows that the phasevarions of multiple NTHI clinical isolates regulate in vitro biofilm formation under disease-specific microenvironmental conditions. The impact of phasevarion regulation was greatest under alkaline conditions that mimic those known to occur in the middle ear during disease. Under alkaline conditions, NTHI strains that express the ModA2 methyltransferase formed biofilms with significantly greater biomass and less distinct architecture than those formed by a ModA2-deficient population. The biofilms formed by NTHI strains that express ModA2 also contained less extracellular DNA (eDNA) and significantly less extracellular HU, a DNABII DNA-binding protein critical for biofilm structural stability. Stable biofilm structure is critical for bacterial pathogenesis and persistence in multiple experimental models of disease. These results identify a role for the phasevarion in regulation of biofilm formation, a process integral to the chronic nature of many infections. Understanding the role of the phasevarion in biofilm formation is critical to the development of prevention and treatment strategies for these chronic diseases. IMPORTANCE Upper respiratory tract infections are the number one reason for a child to visit the emergency department, and otitis media (middle ear infection) ranks third overall. Biofilms contribute significantly to the chronic nature of bacterial respiratory tract infections, including otitis media, and make these diseases particularly difficult to treat. Several mucosa-associated human pathogens utilize a mechanism of rapid adaptation termed the phasevarion, or phase variable regulon, to resist environmental and host immune pressures. In this study, we assessed the role of the phasevarion in regulation of biofilm formation by nontypeable Haemophilus influenzae (NTHI), which causes numerous respiratory tract diseases. We found that the NTHI phasevarion regulates biofilm structure and critical biofilm matrix components under disease-specific conditions. The findings of this work could be significant in the design of improved strategies against NTHI infections, as well as diseases due to other pathogens that utilize a phasevarion.

scholarly journals The Fatty Acid Signaling Moleculecis-2-Decenoic Acid Increases Metabolic Activity and Reverts Persister Cells to an Antimicrobial-Susceptible State

2014 ◽  
Vol 80 (22) ◽  
pp. 6976-6991 ◽  
Author(s):  
Cláudia N. H. Marques ◽  
Aleksey Morozov ◽  
Penny Planzos ◽  
Hector M. Zelaya
Keyword(s):  
Fatty Acid ◽  
Cell Number ◽  
Antimicrobial Treatment ◽  
Bacterial Cells ◽  
Chronic Infections ◽  
Persister Cells ◽  
Decenoic Acid ◽  
Signaling Molecule ◽  
Content Type ◽  
Persister Cell

ABSTRACTPersister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is believed to significantly improve efforts in eradicating biofilm-related, chronic infections. While much research has focused on elucidating the mechanism(s) by which persister cells form, little is known about the mechanism or factors that enable persister cells to revert to an active and susceptible state. Here, we demonstrate thatcis-2-decenoic acid (cis-DA), a fatty acid signaling molecule, is able to change the status ofPseudomonas aeruginosaandEscherichia colipersister cells from a dormant to a metabolically active state without an increase in cell number. This cell awakening is supported by an increase of the persister cells' respiratory activity together with changes in protein abundance and increases of the transcript expression levels of several metabolic markers, includingacpP, 16S rRNA,atpH, andppx. Given that most antimicrobials target actively growing cells, we also explored the effect ofcis-DA on enhancing antibiotic efficacy in killing persister cells due to their inability to keep a persister cell state. Compared to antimicrobial treatment alone, combinational treatments of persister cell subpopulations with antimicrobials andcis-DA resulted in a significantly greater decrease in cell viability. In addition, the presence ofcis-DA led to a decrease in the number of persister cells isolated. We thus demonstrate the ability of a fatty acid signaling molecule to revert bacterial cells from a tolerant phenotype to a metabolically active, antimicrobial-sensitive state.

scholarly journals The CpAL Quorum Sensing System Regulates Production of Hemolysins CPA and PFO To Build Clostridium perfringens Biofilms

2015 ◽  
Vol 83 (6) ◽  
pp. 2430-2442 ◽  
Author(s):  
Jorge E. Vidal ◽  
Joshua R. Shak ◽  
Adrian Canizalez-Roman
Keyword(s):  
Quorum Sensing ◽  
Clostridium Perfringens ◽  
Biofilm Formation ◽  
Extracellular Dna ◽  
Wild Type ◽  
Content Type ◽  
Type C ◽  
Enteritis Necroticans ◽  
Biofilm Structure

Clostridium perfringensstrains produce severe diseases, including myonecrosis and enteritis necroticans, in humans and animals. Diseases are mediated by the production of potent toxins that often damage the site of infection, e.g., skin epithelium during myonecrosis. In planktonic cultures, the regulation of important toxins, such as CPA, CPB, and PFO, is controlled by theC. perfringensAgr-like (CpAL) quorum sensing (QS) system. Strains also encode a functional LuxS/AI-2 system. AlthoughC. perfringensstrains form biofilm-like structures, the regulation of biofilm formation is poorly understood. Therefore, our studies investigated the role of CpAL and LuxS/AI-2 QS systems and of QS-regulated factors in controlling the formation of biofilms. We first demonstrate that biofilm production by reference strains differs depending on the culture medium. Increased biomass correlated with the presence of extracellular DNA in the supernatant, which was released by lysis of a fraction of the biofilm population and planktonic cells. Whereas ΔagrBmutant strains were not able to produce biofilms, a ΔluxSmutant produced wild-type levels. The transcript levels of CpAL-regulatedcpaandpfoAgenes, but notcpb, were upregulated in biofilms compared to planktonic cultures. Accordingly, Δcpaand ΔpfoAmutants, in type A (S13) or type C (CN3685) backgrounds, were unable to produce biofilms, whereas CN3685Δcpbmade wild-type levels. Biofilm formation was restored in complemented Δcpa/cpaand ΔpfoA/pfoAstrains. Confocal microscopy studies further detected CPA partially colocalizing with eDNA on the biofilm structure. Thus, CpAL regulates biofilm formation inC. perfringensby increasing levels of certain toxins required to build biofilms.

scholarly journals Noncatalytic Antioxidant Role forHelicobacter pyloriUrease

2018 ◽  
Vol 200 (17) ◽  
Author(s):  
Alan A. Schmalstig ◽  
Stéphane L. Benoit ◽  
Sandeep K. Misra ◽  
Joshua S. Sharp ◽  
Robert J. Maier
Keyword(s):  
Helicobacter Pylori ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Repair System ◽  
Content Type ◽  
Urease Enzyme ◽  
Catalytic Role ◽  
Methionine Residues ◽  
H Pylori

ABSTRACTThe well-studied catalytic role of urease, the Ni-dependent conversion of urea into carbon dioxide and ammonia, has been shown to protectHelicobacter pyloriagainst the low pH environment of the stomach lumen. We hypothesized that the abundantly expressed urease protein can play another noncatalytic role in combating oxidative stress via Met residue-mediated quenching of harmful oxidants. Three catalytically inactive urease mutant strains were constructed by single substitutions of Ni binding residues. The mutant versions synthesize normal levels of urease, and the altered versions retained all methionine residues. The three site-directed urease mutants were able to better withstand a hypochlorous acid (HOCl) challenge than a ΔureABdeletion strain. The capacity of purified urease to protect whole cells via oxidant quenching was assessed by adding urease enzyme to nongrowing HOCl-exposed cells. No wild-type cells were recovered with oxidant alone, whereas urease addition significantly aided viability. These results suggest that urease can protectH. pyloriagainst oxidative damage and that the protective ability is distinct from the well-characterized catalytic role. To determine the capability of methionine sulfoxide reductase (Msr) to reduce oxidized Met residues in urease, purifiedH. pyloriurease was exposed to HOCl and a previously described Msr peptide repair mixture was added. Of the 25 methionine residues in urease, 11 were subject to both oxidation and to Msr-mediated repair, as identified by mass spectrometry (MS) analysis; therefore, the oxidant-quenchable Met pool comprising urease can be recycled by the Msr repair system. Noncatalytic urease appears to play an important role in oxidant protection.IMPORTANCEChronicHelicobacter pyloriinfection can lead to gastric ulcers and gastric cancers. The enzyme urease contributes to the survival of the bacterium in the harsh environment of the stomach by increasing the local pH. In addition to combating acid,H. pylorimust survive host-produced reactive oxygen species to persist in the gastric mucosa. We describe a cyclic amino acid-based antioxidant role of urease, whereby oxidized methionine residues can be recycled by methionine sulfoxide reductase to again quench oxidants. This work expands our understanding of the role of an already acknowledged pathogen virulence factor and specifically expands our knowledge ofH. pylorisurvival mechanisms.

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