Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

Due to the wide application of silver-containing dressings and silver-coated medical devices in clinical treatment; the extensive use of antibacterial agents and heavy metal agents in feed factories, Escherichia coli has formed the tolerance to silver ions. To systematically understand the known silver ion resistance mechanisms of E. coli, this article reviews the complex regulatory network and various physiological mechanisms of silver ion tolerance in E. coli, including the regulation of outer membrane porins, energy metabolism modulation, the role of efflux systems, motility regulation, and silver ion reduction. E. coli reduces the influx of silver ions by missing or mutating outer membrane porins such as OmpR, OmpC, and OmpF. It adapts to high concentrations of silver ions by altering the expression of ArcA/B and enhances the efflux capacity of silver ions under high-concentration silver stress via the endogenous Cus system and exogenous Sil system. Furthermore, the motility of bacteria is related to silver tolerance. E. coli has the ability to reduce silver ions, thereby alleviating the oxidative stress induced by silver ions. These findings provide a new perspective for understanding the formation and spread of bacterial tolerance and provide directions for the development of next-generation silver-based antimicrobials and therapies.
Escherichia coli/genetics* ; Silver/pharmacology* ; Drug Resistance, Bacterial ; Anti-Bacterial Agents/pharmacology* ; Porins/metabolism*

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*

Objective: To explore the changes in bacterial community structure, antibiotic resistance genome, and pathogen virulence genome in river water before and after the river flowing through Haikou City and their transmission and dispersal patterns and to reveal anthropogenic disturbance's effects on microorganisms and resistance genes in the aquatic environment. Methods: The Nandu River was divided into three study areas: the front, middle and rear sections from the upstream before it flowed through Haikou City to the estuary. Three sampling sites were selected in each area, and six copies of the sample were collected in parallel at each site and mixed for 3 L per sample. Microbial community structure, antibiotic resistance, virulence factors, and mobile genetic elements were analyzed through bioinformatic data obtained by metagenomic sequencing and full-length sequencing of 16S rRNA genes. Variations in the distribution of bacterial communities between samples and correlation of transmission patterns were analyzed by principal co-ordinates analysis, procrustes analysis, and Mantel test. Results: As the river flowed through Haikou City, microbes' alpha diversity gradually decreased. Among them, Proteobacteria dominates in the bacterial community in the front, middle, and rear sections, and the relative abundance of Proteobacteria in the middle and rear sections was higher than that in the front segment. The diversity and abundance of antibiotic resistance genes, virulence factors, and mobile genetic elements were all at low levels in the front section and all increased significantly after flow through Haikou City. At the same time, horizontal transmission mediated by mobile genetic elements played a more significant role in the spread of antibiotic-resistance genes and virulence factors. Conclusions: Urbanization significantly impacts river bacteria and the resistance genes, virulence factors, and mobile genetic elements they carry. The Nandu River in Haikou flows through the city, receiving antibiotic-resistant and pathogen-associated bacteria excreted by the population. In contrast, antibiotic-resistant genes and virulence factors are enriched in bacteria, which indicates a threat to environmental health and public health. Comparison of river microbiomes and antibiotic resistance genomes before and after flow through cities is a valuable early warning indicator for monitoring the spread of antibiotic resistance.
Humans ; Rivers ; Virulence Factors/genetics* ; RNA, Ribosomal, 16S/genetics* ; Microbiota/genetics* ; Anti-Bacterial Agents ; Drug Resistance, Microbial/genetics*

To explore the clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), in order to provide reference for the prevention and treatment of CRKP infection. Retrospective analysis was performed on 510 clinical isolates of CRKP from January 2017 to December 2021, and strain identification and drug sensitivity tests were conducted by MALDI-TOF mass spectrometer and VITEK-2 Compact microbial drug sensitivity analyzer. The carbapenemase phenotype of CRKP strain was detected by carbapenemase inhibitor enhancement test. The CRKP strain was further categorized by immunochromogenic method and polymerase chain reaction (PCR) was used for gene detection. The results showed that 302 strains (59.2%) were derived from sputum, 127 strains (24.9%) from urine and 47 strains (9.2%) from blood. 231 (45.3%) were mainly distributed in intensive care, followed by 108 (21.2%) in respiratory medicine and 79 (15.5%) in neurosurgery. Drug susceptibility test result shows that the resistant rate of tigecycline increased from 1.0% in 2017 to 10.1% in 2021, the difference was statistically significant (χ²=14.444,P<0.05). The results of carbapenemase inhibitor enhancement test showed that 461 carbapenemase strains (90.4%) of 510 CRKP strains, including 450 serinase strains (88.2%), 9 metalloenzyme strains (1.8%), and 2 strains (0.4%) produced both serine and metalloenzyme. 49 strains (9.6%) did not produce enzymes. Further typing by immunochromogenic assay showed that 461 CRKP strains were KPC 450 (97.6%) and IMP 2 (0.4%). 7 NDM (1.5%); 2 strains of KPC+NDM (0.4%); PCR results were as follows: 450 strains of blaKPC (97.6%), 2 strains of blaIMP (0.4%), 7 strains of blaNDM (1.5%), and 2 strains of blaKPC+NDM (0.4%). In conclusion, CRKP strains mainly originated from sputum specimens and distributed in intensive care department, and the drug resistance characteristics were mainly KPC type in carbapenemase production. Clinical microbiology laboratory should strengthen the monitoring of CRKP strains, so as to provide reference for preventing CRKP infection and reducing the production of bacterial drug resistance.
Anti-Bacterial Agents/pharmacology* ; Carbapenems/pharmacology* ; Klebsiella pneumoniae/genetics* ; Hospital Distribution Systems ; Retrospective Studies ; Microbial Sensitivity Tests ; beta-Lactamases/genetics* ; Bacterial Proteins/genetics* ; Drug Resistance, Bacterial/genetics*

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

OBJECTIVE: To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data. METHODS: Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS). RESULTS: This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24). CONCLUSION We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
Humans ; Escherichia coli/genetics* ; Escherichia coli Infections/epidemiology* ; Multilocus Sequence Typing ; Genotype ; Beijing ; Drug Resistance, Multiple, Bacterial/genetics* ; Anti-Bacterial Agents/pharmacology* ; Diarrhea ; Microbial Sensitivity Tests

Stenotrophomonas species are non-fermentative Gram-negative bacteria that are widely distributed in environment and are highly resistant to numerous antibiotics. Thus, Stenotrophomonas serves as a reservoir of genes encoding antimicrobial resistance (AMR). The detection rate of Stenotrophomonas is rapidly increasing alongside their strengthening intrinsic ability to tolerate a variety of clinical antibiotics. This review illustrated the current genomics advances of antibiotic resistant Stenotrophomonas, highlighting the importance of precise identification and sequence editing. In addition, AMR diversity and transferability have been assessed by the developed bioinformatics tools. However, the working models of AMR in Stenotrophomonas are cryptic and urgently required to be determined. Comparative genomics is envisioned to facilitate the prevention and control of AMR, as well as to gain insights into bacterial adaptability and drug development.
Stenotrophomonas/genetics* ; Drug Resistance, Bacterial/genetics* ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Genomics ; Microbial Sensitivity Tests

Objective: To investigate the antimicrobial resistance of food-borne diarrheagenic Escherichia coli (DEC) and the prevalence of mcr genes that mediates mobile colistin resistance in parts of China, 2020. Methods: For 91 DEC isolates recovered from food sources collected from Fujian province, Hebei province, Inner Mongolia Autonomous Region and Shanghai city in 2020, Vitek2 Compact biochemical identification and antimicrobial susceptibility testing platform was used for the detection of antimicrobial susceptibility testing (AST) against to 18 kinds of antimicrobial compounds belonging to 9 categories, and multi-polymerase chain reaction (mPCR) was used to detect the mcr-1-mcr-9 genes, then a further AST, whole genome sequencing (WGS) and bioinformatics analysis were platformed for these DEC isolates which were PCR positive for mcr genes. Results: Seventy in 91 isolates showed different antimicrobial resistance levels to the drugs tested with a resistance rate of 76.92%. The isolates showed the highest antimicrobial resistance rates to ampicillin (69.23%, 63/91) and trimethoprim-sulfamethoxazole (59.34%, 54/91), respectively. The multiple drug-resistant rate was 47.25% (43/91). Two mcr-1 gene and ESBL (extended-spectrum beta-lactamase) positive EAEC (enteroaggregative Escherichia coli) strains were detected. One of them was identified as serotype of O11:H6, which showed a resistance profile to 25 tested drugs referring to 10 classes, and 38 drug resistance genes were predicted by genome analysis. The other one was O16:H48 serotype, which was resistant to 21 tested drugs belonging to 7 classes and carried a new variant of mcr-1 gene (mcr-1.35). Conclusion: An overall high-level antimicrobial resistance was found among foodborne DEC isolates recovered from parts of China in 2020, and so was the MDR (multi-drug resistance) condition. MDR strains carrying multiple resistance genes such as mcr-1 gene were detected, and a new variant of mcr-1 gene was also found. It is necessary to continue with a dynamic monitoring on DEC contamination and an ongoing research into antimicrobial resistance mechanisms.
Humans ; Colistin/pharmacology* ; Anti-Bacterial Agents/pharmacology* ; Escherichia coli Infections/epidemiology* ; Escherichia coli Proteins/genetics* ; Drug Resistance, Bacterial/genetics* ; China/epidemiology* ; Escherichia coli ; Plasmids/genetics* ; Microbial Sensitivity Tests

Humans ; Isoniazid/pharmacology* ; Mycobacterium tuberculosis/genetics* ; Rifampin/pharmacology* ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Tuberculosis, Multidrug-Resistant/microbiology* ; Drug Resistance, Multiple, Bacterial/genetics* ; Bacterial Proteins/genetics*