Genomic population structure of <i>Helicobacter pylori</i> Shanghai isolates and identification of genomic features uniquely linked with pathogenicity

Feng, Yang; Zhang, Jinghao; Su, Wang; Sun, Zhaoyang; Zhou, Jun; Li, Feng; Liu, Yue; Liu, Yixin; Chi, Wenjing; Liu, Tao; He, Yongqun; Xiang, Ping; Bao, Zhijun; Olszewski, Michal A.; Hu, Zhao; Zhang, Yanmei

doi:10.1080/21505594.2021.1920762

Cited by 7 publications

(5 citation statements)

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“…Among them, 49 samples clustered with hpEastAsia, 3 were hpEurope, and 2 were hpNEAfrica ( Figure 1 ). Considering Shanghai as an international hub, the 5 strains from outside hpEastAsia may be associated with increased human mobility and large-scale international export of food products ( Yang et al, 2021 ). Compared to the RdxA reference, mutations, such as T31E, H53R, D59N, L62V, S88P, G98S, R131K, and V172I ( Table 3 ), were conservatively present in >68% of RdxA sequences.…”

Section: Resultsmentioning

confidence: 99%

Functional determination of site-mutations in rdxA involved in metronidazole resistance of Helicobacter pylori

Huang,

Li,

et al. 2024

Front. Cell Dev. Biol.

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BackgroundMetronidazole (MTZ) is among the first-line drugs against the human gastric pathogen Helicobacter pylori (H. pylori). MTZ is used as a prodrug that is activated by an oxygen-insensitive enzyme NADPH nitroreductase (RdxA). Loss-of-function mutations in rdxA make H. pylori MTZ resistant; however, experimental proof is lacking.MethodsWe collected 139 gastric biopsy samples from patients suspected of H. pylori infection in Shanghai, and amplified Hp-specific rdxA gene from 134 samples. All these rdxA genes were sequenced and phylogenetically compared. The effect of mutations on RdxA function was measured by expressing them in Escherichia coli DH5α by using the MTZ sensitivity test.ResultsIn total, 134 gastric biopsy samples were identified as H. pylori positive. Of the 134 samples, 74 and 6 had point mutations at the various sites or promoter region of rdxA, generating truncated and extended fused proteins, respectively. The remaining 54 were full-length with single nucleotide variation (SNV) compared with the wild-type RdxA from H. pylori, with 49 clustering with hpEastAsia, 3 with hpEurope, and 2 with hpNEAfrica. All 134 rdxA were expressed in E. coli DH5α; 22 and 112 resultant strains showed MTZ-sensitive and MTZ-resistant phenotypes, respectively. Comparative analysis of single nucleotide polymorphisms (SNPs) in the functional and inactivated RdxA revealed 14 novel mutations in RdxA, 5 of which conferred MTZ resistance: S18F, D59S, L62I, S79N, and A187V.ConclusionThe occurrence of MTZ resistance induced by site-mutation of RdxA in patients with H. pylori infection was 83.6% (112/134) in the Shanghai region. The major form of loss-of-function mutation was truncation of RdxA translation at a rate of 58/112 (51.8%). Molecular detection reliably determined the resistance of H. pylori to MTZ. Thus, the functional mutants involved in MTZ resistance facilitate clinical diagnosis and medication based on sequence analysis.

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Section: Resultsmentioning

confidence: 99%

Functional determination of site-mutations in rdxA involved in metronidazole resistance of Helicobacter pylori

Huang,

Li,

et al. 2024

Front. Cell Dev. Biol.

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“…Antibiotic resistance associated genes including multidrug efflux system protein, multidrug ABC transporter protein, b-lactamase protein, and DNA topoisomerase protein were detected in the CARD database. The detailed genomic features are listed in Table 2 (Gan et al, 2020;Yang et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

First Study of Bacteremia Caused by Herbaspirillum huttiense in China: A Brief Research Report and Literature Review

Bao

Qiao

et al. 2022

Front. Cell. Infect. Microbiol.

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Bacteremia caused by Herbaspirillum huttiense (H. huttiense) is relatively rare in positive blood cultures. H. huttiense is an opportunistic bacterium in patients with cancer and cirrhosis and has also been described in immunocompromised hosts. In this study, H. huttiense was isolated from a patient with repeated chest tightness and chest pain. Smears were prepared, stained, and examined by microscopy. Single colonies were analyzed by Gram staining, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA sequencing and Next-Generation Sequencing (NGS). Antibiotic sensitivity was assessed by agar dilution. Almost all publications on H. huttiense infections in the PubMed/ScienceDirect/EBSCO databases were reviewed and summarized. Blood sample culturing yielded white, gelatinous, and slightly raised colonies without hemolytic rings. The bacilli were found to be Gram-negative, and MS results showed 99.2% homology with H. huttiense. This was confirmed by 16S rRNA gene sequencing, phylogenetic tree analysis and NGS all of which were homologous with H. huttiense in GenBank. Antibiotic susceptibility tests were performed to determine the minimum inhibitory concentrations (MICs) of imipenem, meropenem, piperacillin-tazobactam, and levofloxacin. A comprehensive literature review revealed that H. huttiense was an emergent pathogen. After medical treatment, the patient’s body temperature returned to normal. This is the first report of bacteremia caused by H. huttiense in China. The findings could improve the awareness and attention of the rare pathogenic microorganisms in China.

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“…Genomic islands (GIs) of prokaryotes are discrete inserted DNA segments obtained by horizontal transfer which carries genes that could affect pathogenicity, antibiotic resistance, metabolism, and adaptability (31)(32)(33). Compared with Pm3, the GIs of Pm64 had lost some genes involved in trehalose metabolism (treB, treC and treR).…”

Section: Discussionmentioning

confidence: 99%

“…In microbial infections, the virulence genes are the major determinants of disease severity ( 33 ). In explaining the mechanism of Pm64 virulence attenuation, more attention should be attached to the level of gene expression in addition to the presence or absence of virulence genes.…”

Section: Discussionmentioning

confidence: 99%

Genomic and Transcriptomic Analysis of Bovine Pasteurella multocida Serogroup A Strain Reveals Insights Into Virulence Attenuation

et al. 2021

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Pasteurella multocida is one of the primary pathogens of bovine respiratory disease (BRD), and causes huge losses in the cattle industry. The Pm3 strain was a natural isolate, which is a strong form of pathogen and is sensitive to fluoroquinolones antibiotics. A high fluoroquinolone resistant strain, Pm64 (MIC = 64 μg/mL), was formed after continuous induction with subinhibitory concentration (1/2 MIC) of enrofloxacin, with the enhanced growth characteristics and large attenuation of pathogenicity in mice. This study reports the whole genome sequence and the transcription profile by RNA-Seq of strain Pm3/Pm64. The results showed an ineffective difference between the two strains at the genome level. However, 32 genes could be recognized in the gene islands (GIs) of Pm64, in which 24 genes were added and 8 genes were lost. Those genes are involved in DNA binding, trehalose metabolism, material transportation, capsule synthesis, prophage, amino acid metabolism, and other functions. In Pm3 strain, 558 up-regulated and 568 down-regulated genes were found compared to Pm64 strain, from which 20 virulence factor-related differentially expressed genes (DEGs) were screened. Mainly differentially transcribed genes were associated with capsular polysaccharide (CPS), lipopolysaccharide (LPS), lipooligosaccharide (LOS). Iron utilization, and biofilm composition. We speculated that the main mechanism of virulence attenuation after the formation of resistance of Pm64 comes from the change of the expression profile of these genes. This report elucidated the toxicity targets of P. multocida serogroup A which provide fundamental information toward the understanding of the pathogenic mechanism and to decreasing antimicrobial drugs resistance.

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Genomic population structure of Helicobacter pylori Shanghai isolates and identification of genomic features uniquely linked with pathogenicity

Cited by 7 publications

References 54 publications

Functional determination of site-mutations in rdxA involved in metronidazole resistance of Helicobacter pylori

Functional determination of site-mutations in rdxA involved in metronidazole resistance of Helicobacter pylori

First Study of Bacteremia Caused by Herbaspirillum huttiense in China: A Brief Research Report and Literature Review

Genomic and Transcriptomic Analysis of Bovine Pasteurella multocida Serogroup A Strain Reveals Insights Into Virulence Attenuation

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