Antibiotic resistance is a major global health concern, and inappropriate antibiotic use contributes significantly to the development of resistance in pathogens. Bacteroides fragilis, an anaerobic bacterium, is commonly treated with β-lactam antibiotics like meropenem. B. fragilis possesses various antibiotic resistance mechanisms, including enzymatic modification of antibiotics, efflux systems, and reduction of cell membrane permeability. The primary mechanism of carbapenem resistance in B. fragilis is linked to the production of a metallo-β-lactamase encoded by the cfiA gene. However, this gene is frequently inactive and requires activation by insertion elements. The study aimed to explore the expression of specific genes in B. fragilis associated with different metabolic pathways in response to exposure to sub-inhibitory concentrations of meropenem. The study used B. fragilis strain BFR KZ01, obtained from a patient with appendicitis and peritonitis. Serial exposure to meropenem was conducted, and gene expression was analyzed using quantitative RT-PCR. Significant and long-lasting alterations in gene expression patterns were observed in B. fragilis following exposure to meropenem, even after removal of the antibiotic. Genes such as cfiA, oxyR, and Ddl showed heightened expression levels even after discontinuation of meropenem. The study discussed the implications of gene expression changes induced by meropenem exposure, highlighting the role of oxidative stress response (oxyR), D-Ala-D-Ala ligase (Ddl), and carbapenemase (cfiA) genes in antibiotic resistance mechanisms. The study concluded that exposure to meropenem induced lasting alterations in gene expression in B. fragilis, contributing to antibiotic resistance. Understanding these mechanisms is crucial for developing strategies to combat antibiotic resistance.

This study aimed to assess the susceptibility of a clinical strain of Bacteroides fragilis (BFR_KZ01) from Kazakhstan, a significant anaerobic pathogen in human infections, to commonly used anti-anaer-obic drugs at the local level. Additionally, the research aimed to identify genes with MALDI-TOF/MS associated with antibiotic resistance. To perform surveillance of cfiA-positive Bacteroides fragilis using new subtyping software module, MALDI Biotyper Subtyping Module, on MALDI-TOF MS system, and to evaluate the detection ability of the module.The bacterial isolate was identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene sequencing. Suscepti-bility to broad-spectrum antibiotics (metronidazole, meropenem, ciprofloxacin, clindamycin, and tet-racycline) for intra-abdominal infections treatment was determined. ClinProTools 3.0.22 software was employed to analyze mass spectra groups crucial for identifying cfiA-positive strains. MALDI-TOF/MS analysis classified strain BFR_KZ01 into Group II (cfiA-positive), despite being phenotypically sensi-tive to meropenem (mean MIC, 1.3 mg/L). The study identified drug resistance determinants in strain BFR_KZ01, demonstrating its multidrug-resistant nature due to carrying nimB, tetQ, and gyrA genes, conferring resistance to metronidazole, tetracycline, and ciprofloxacin.

Колоректальный рак (КРР) является одним из самых распространенных заболеваний в мире и занимает второе место по смертности. Каждый год в Казахстане регистрируются 3000 новых случаев КРР. Большинство случаев данного заболевания не являются генетически детерминированными, а возникают спонтанно за счет влияния внешних факторов, к одному из которых относится нарушение баланса кишечной микрофлоры в пользу патогенных бактерий. Одним из таких патогенов, чья роль в патогенезе рака толстого кишечника находит все больше доказательств в исследованиях последних лет является pks+ E. coli. Геномный остров поликетидсинтетазы кодирует колибактин - генотоксин, относящийся к группе цикломодулинов, способный вызывать двуцепочечные разрывы ДНК, хромосомные абберации и блокировать эукариотический клеточный цикл. Колибактин-продуцирующие штаммы кишечной палочки могут создавать провоспалительную и проканцерогенную микросреду на слизистой оболочке толстого кишечника, а также модулировать иммунные реакции хозяина. В данной обзорной статье рассмотрена роль кишечной микробиоты, в частности pks+ E. coli в развитии и прогрессировании рака толстого кишечника, а также возможные терапевтические стратегии по профилактики и лечению этого заболевания

This review discusses multi-omics (genomic, transcriptomic, and proteomic) approaches for studying bacteria of the Bacteroides spp. group, which are the most common anaerobes in the human colon and are responsible for over half of all intra-abdominal anaerobic infections. These multi-omics approaches have enabled the identification of virulence factors, antimicrobial resistance genes, and other functional elements of the Bacteroides genome. This information is crucial for understanding the pathogenic potential of these bacteria and their role in the development of anaerobic infections. This review examines the transcriptional response of Bacteroides after exposure to sub-inhibitory concentrations of antimicrobial drugs, as well as the main methods of proteomic analysis and achievements in studying the Bacteroides proteome. Overall, the modern perspectives of multi-omics studies on Bacteroides emphasize the possibility of integrating different omics approaches for a more comprehensive understanding of their biology, functional characteristics, and ecological roles in the gut ecosystem.

In recent years, increasing evidence has confirmed the importance of intestinal dysbiosis in the development and progression of colorectal cancer (CRC). Particular attention is paid to colibactin-producing Escherichia coli, which is considered one of the key microbial factors in carcinogenesis. Colibactin-producing Escherichia coli carries the pks pathogenicity island encoding the low-molecular genotoxin colibactin. This toxin has a pronounced cytotoxic effect on intestinal epithelial cells, causing double-strand DNA breaks and cell cycle arrest. Such damage contributes to the development of genomic instability, which ultimately increases the risk of colorectal cancer. The aim of our study was to determine the clinical role of pks+ E. coli in the development and progression of CRC in Kazakhstani patients. Biopsies of the intestinal mucosa were obtained from 113 patients of the National Scientific Oncology Center with a confirmed diagnosis of colorectal adenocarcinoma from three sites (tumor, adjacent tumor-unaltered area, and distally located healthy area). To detect marker genes of colibactin (clbA, clbB, clbQ) in the selected biomaterial, quantitative PCR and routine PCR methods were used. A comprehensive assessment of the relationship between the carriage of pks+ Escherichia coli and such factors as tumor size and location, consumption of red and processed meat, the presence of bad habits, as well as metabolic and somatic diseases in patients was carried out. Our results demonstrated that colibactin-producing E. coli was detected in 60% of tumor tissue biopsies, 53% of tumor-adjacent samples, and 54% of distal intestinal mucosa biopsies in cancer patients (P> 0.05). A statistically significant relationship was found between pks+ Escherichia coli carriage and tumor size in patients with CRC (P=0.009). This may indicate that pathogenic E. coli strains act not only as driver microorganisms initiating colon carcinogenesis, but also as potential long-term colonizers of tumor tissue involved in the pathogenesis and progression of the disease at later stages.