SpoT-Mediated NapA Upregulation Promotes Oxidative Stress-Induced Helicobacter pylori Biofilm Formation and Confers Multidrug Resistance

Zhao, Yican; Cai, Yukui; Chen, Zhenghong; Li, Huanjie; Xu, Zhengzheng; Li, Wenjuan; Jia, Jihui; Sun, Yuan

doi:10.1128/aac.00152-21

Cited by 25 publications

(25 citation statements)

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“…The expression of adhesins increases during the transition from the planktonic to the biofilm phase ( Krzyżek et al, 2020 ). Several studies have shown that adhesive proteins, such as NapA , AlpB , SabA , BabA , Homb , LabA and HopZ are involved in biofilm formation ( Cooksley et al, 2003 ; Yang et al, 2011 ; Acio-Pizzarello et al, 2017 ; Servetas et al, 2018 ; Zhao et al, 2021 ). Compared to wild-type strains, ArsRS mutants had high surface attachment and biofilm production, and the expression of genes encoding outer membrane proteins was increased in these mutants, including AlpB , SabA , BabA , Homb , LabA and HopZ ( Acio-Pizzarello et al, 2017 ; Servetas et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…NapA is a surface protein that attracts and activates neutrophils and promotes endothelial adhesion and production of oxygen radicals and chemokines ( D’Elios et al, 2007 ). When Helicobacter pylori is exposed to oxidative stress, NapA is highly expressed to resist oxygen stress injury, thus relieving bacterial survival pressure and promoting the formation and aggregation of EPS to promote biofilm formation ( Cooksley et al, 2003 ; Zhao et al, 2021 ). Another study also showed that NapA plays a role in adhesion to a substratum and H. pylori and hence influences biofilm formation ( Yang et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

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Revealing the novel effect of Jinghua Weikang capsule against the antibiotic resistance of Helicobacter pylori

et al. 2022

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BackgroundHelicobacter pylori (H. pylori) infects half of the human population globally. Eradication rates with triple or quadruple therapy have decreased owing to the increasing rate of antibiotic resistance. Jinghua Weikang capsule (JWC) is the first and most popular Chinese patent medicine approved by the state for the treatment of gastritis and peptic ulcers caused by H. pylori infection in China. Previous studies have found that JWC has a certain bactericidal effect on drug-resistant H. pylori and its major component, Chenopodium ambrosioides L. inhibits biofilm formation, but the mechanism remains unclear. This study focused on drug-resistant H. pylori and explored whether JWC could reverse drug resistance and its related mechanisms.MethodThe agar plate dilution method, E-test method, and killing kinetics assay were used to evaluate the bactericidal effect of JWC on antibiotic-resistant H. pylori and its effect on antibiotic resistance. Sanger sequencing was used to detect mutations in drug resistance genes. The crystal violet method, scanning electron microscopy, and confocal laser scanning microscopy were used to evaluate the effects of JWC on biofilms. qPCR was performed to evaluate the effect of JWC on the expression of efflux pump-related genes. qPCR and immunofluorescence were used to evaluate the effects of JWC on H. pylori adhesion.ResultsJWC showed considerable antibacterial activity against drug-resistant H. pylori strains, with minimum inhibitory concentration (MIC) values ranging from 64 to 1,024 μg/ml. The MIC of metronidazole (MTZ) against H. pylori 26,695–16R decreased from 64 to 6 μg/ml after treatment with 1/2 MIC of JWC. The resistance of H. pylori 26,695–16R to MTZ was reversed by JWC, and its effect was better than that of PaβN and CCCP. H. pylori 26,695–16R is a moderate biofilm-forming strain, and JWC (16–64 μg/ml) can inhibit the formation of biofilms in H. pylori 26,695–16R. JWC reduced the expression of HP0605-HP0607 (hefABC), HP0971-HP0969 (hefDEF), HP1327-HP1329 (hefGHI), and HP1489-HP1487. JWC reduced the adhesion of H. pylori to GES-1 cells and the expression of adhesives NapA, SabA, and BabA.ConclusionThe reversal of MTZ resistance by JWC may be achieved through the adhesin/efflux pump-biofilm pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Revealing the novel effect of Jinghua Weikang capsule against the antibiotic resistance of Helicobacter pylori

et al. 2022

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“… 27 SpoT has been implicated in biofilm formation in multi-drug resistant bacteria by upregulating the efflux pump HP1174 and the neutrophil-activating protein (NapA; HP0243). 28 , 29 The transporter proteins HP0939, HP0497, and HP0471 are implicated in H. pylori biofilm formation. 30 …”

Section: Helicobacter Pylori Biofilmmentioning

confidence: 99%

Helicobacter pylori Biofilm-Related Drug Resistance and New Developments in Its Anti-Biofilm Agents

Hou¹,

Yin²,

Wang³

et al. 2022

IDR

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Helicobacter pylori is one of the most common pathogenic bacterium worldwide, infecting about 50% of the world’s population. It is a major cause of several upper gastrointestinal diseases, including peptic ulcers and gastric cancer. The emergence of H. pylori resistance to antibiotics has been a major clinical challenge in the field of gastroenterology. In the course of H. pylori infection, some bacteria invade the gastric epithelium and are encapsulated into a self-produced matrix to form biofilms that protect the bacteria from external threats. Bacteria with biofilm structures can be up to 1000 times more resistant to antibiotics than planktonic bacteria. This implies that targeting biofilms might be an effective strategy to alleviate H. pylori drug resistance. Therefore, it is important to develop drugs that can eliminate or disperse biofilms. In recent years, anti-biofilm agents have been investigated as alternative or complementary therapies to antibiotics to reduce the rate of drug resistance. This article discusses the formation of H. pylori biofilms, the relationship between biofilms and drug resistance in H. pylori , and the recent developments in the research of anti-biofilm agents targeting H. pylori drug resistance.

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“…Biofilms can enhance resistance to antibiotics, improve the persistence and survival rate in the host, and reduce the success rate of treatment [ 5 ]. At present, the regulatory process of H. pylori biofilm formation has not been fully explained, and in particular, transcriptome research on H. pylori biofilms remains limited [ 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis of the Response of Mature Helicobacter pylori Biofilm to Different Doses of Lactobacillus salivarius LN12 with Amoxicillin and Clarithromycin

Jin

Yang

2022

Antibiotics

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Helicobacter pylori is a gastrointestinal pathogen with a high infection rate. Probiotics are clinically used as an adjuvant to improve the cure rate and reduce the side effects of antibiotic treatment for H. pylori. This study is the first to explore the effects of a cell-free supernatant of high- or low-dose Lactobacillus salivarius LN12 combined with amoxicillin (AMX) and clarithromycin (CLR) on H. pylori 3192 biofilms in terms of the biofilm biomass, survival rates, biofilm structure, and transcriptome. The results showed that the combination of the CFS of high-dose LN12 with AMX and CLR had stronger effects on the biofilm biomass, survival rate, and structure of H. pylori 3192 biofilms. H. pylori 3192 biofilms may increase the expression of NADH-related genes and downregulate flagellar assembly and quorum sensing-related receptor genes to deal with the stronger stress effects of high-dose LN12 with AMX and CLR. In conclusion, the biofilm biomass, survival rate, structure, and transcriptome results showed that the combination of LN12 CFS with AMX and CLR had dose effects. We recommend that compared with low doses, high doses of L. salivarus LN12 combined with AMX and CLR may be more effective for H. pylori biofilm than low doses.

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SpoT-Mediated NapA Upregulation Promotes Oxidative Stress-Induced Helicobacter pylori Biofilm Formation and Confers Multidrug Resistance

Cited by 25 publications

References 73 publications

Revealing the novel effect of Jinghua Weikang capsule against the antibiotic resistance of Helicobacter pylori

Revealing the novel effect of Jinghua Weikang capsule against the antibiotic resistance of Helicobacter pylori

Helicobacter pylori Biofilm-Related Drug Resistance and New Developments in Its Anti-Biofilm Agents

Transcriptome Analysis of the Response of Mature Helicobacter pylori Biofilm to Different Doses of Lactobacillus salivarius LN12 with Amoxicillin and Clarithromycin

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