Drug Resistance Characteristics Research Articles

Population structure of the B0/W148 Mycobacterium tuberculosis subtype: Phylogenetic analysis and characteristics of genotypic drug resistance

Background. The B0/W148 subtype belongs to the L2phylogenetic lineage of Mycobacterium tuberculosis and is most common in the former Soviet Union. Test systems capable of detecting genetic variants of the pathogen are needed for effective epidemiological surveillance. Studying the genetic diversity of B0/W148 strains and finding molecular markers suitable for their genotyping are key steps in the development of such diagnostic tools.The aim of the work. To study the phylogenetic diversity of the B0/W148 subtype circulating in the territory of the Russian Federation and neighboring countries in order to identify unique clades and search for specific molecular markers suitable for their precise identification.Materials and methods. The study used DNA samples of B0/W148 strains (n = 34) isolated in different regions of the Russian Federation, as well as genomic data obtained from the SRA NCBI (Sequence Read Archive of the National Center for Biotechnology Information) (n = 419). Phylogenetic analysis and principal component analysis (PCA) of whole genome sequencing (WGS) data were used to analyze genetic diversity and to identify molecular markers. An evolutionary reconstruction of the age of the identified clades was carried out.Results. The analysis of the B0/W148 genomes (n = 453) revealed that they are divided into three phylogenetic clades: B – basal, M – minor and P – principal. It was found that specific mutations in the M and P clades allow for their differential diagnosis. The 4137219T>G mutation is unique for the M clade, and the 2241091C>T mutation is unique for the P clade. No characteristic mutations were found among the strains of B clade. In addition, unique mutation profiles in the genes responsible for drug resistance were identified for the clades.Conclusion. The study showed that B0/W148 strains represent a genetically heterogeneous population divided into B, M and P clades. M and P Clades have unique mutations that allow for their identification. It was also found that all clades are characterized by the presence of specific mutation profiles in drug resistance genes.

Antimicrobial Resistance and Public Health Risks Associated with Staphylococci Isolated from Raw and Processed Meat Products.

This study aimed at evaluating the occurrence, antibiotic resistance, and β-lactamase production in Staphylococcus isolates recovered from meat and meat products, as well as the incidence of antimicrobial resistance (AMR) genes in these bacterial isolates. The prevalence of Staphylococcus was very high (75% and 50%) in street kebab and raw buffalo meat, respectively. The antibiotic resistance and susceptibility behavior showed that 82% of the Staphylococcus isolates were resistant to β-lactam antibiotics such as aztreonam, followed by methicillin (68%), oxacillin (54%), cefepime (36%), ceftazidime (34%), cefaclor (24%), cefotaxime (22%), ertapenem (4%), meropenem and imipenem (2%). Among non-β-lactam antibiotics, the most widespread resistance was observed against nalidixic acid (80%), sulfadiazine (76%), vancomycin (24%), erythromycin (10%), chloramphenicol (6%), and kanamycin and gatifloxacin (4%). One hundred percent of the isolates were susceptible to ciprofloxacin, tetracycline, gemifloxacin, and cefotaxime/clavulanic acid. In vitro drug-resistant characteristics revealed 36 distinct resistance patterns of Staphylococcus isolates, with 82% of them being multidrug resistant (MDR). Iodometric assay showed that 48% of the Staphylococcus isolates produced β-lactamase and 24% of the isolates were capable of producing extended-spectrum beta-lactamases phenotypically. The most commonly detected AMR gene was mecA (29.2%), followed by Sul 1 (25%) and qnrS and qnrB (20.8%), in Staphylococcus isolates. Current findings show widespread occurrence of MDR Staphylococcus strains in raw meat and street meat products, which is a potential risk to public health. Therefore, the study suggests strict monitoring of hygiene through the whole food chain and judicious use of antibiotics.

Targeting Molecular Signaling Pathways and Cytokine Responses to Modulate c-MYC in Acute Myeloid Leukemia.

Overexpression of the MYC oncogene, encoding c-MYC protein, contributes to the pathogenesis and drug resistance of acute myeloid leukemia (AML) and many other hematopoietic malignancies. Although standard chemotherapy has predominated in AML therapy over the past five decades, the clinical outcomes and patient response to treatment remain suboptimal. Deeper insight into the molecular basis of this disease should facilitate the development of novel therapeutics targeting specific molecules and pathways that are dysregulated in AML, including fms-like tyrosine kinase 3 (FLT3) gene mutation and cluster of differentiation 33 (CD33) protein expression. Elevated expression of c-MYC is one of the molecular features of AML that determines the clinical prognosis in patients. Increased expression of c-MYC is also one of the cytogenetic characteristics of drug resistance in AML. However, direct targeting of c-MYC has been challenging due to its lack of binding sites for small molecules. In this review, we focused on the mechanisms involving the bromodomain and extra-terminal (BET) and cyclin-dependent kinase 9 (CDK9) proteins, phosphoinositide-Akt-mammalian target of rapamycin (PI3K/AKT/mTOR) and Janus kinase-signal transduction and activation of transcription (JAK/STAT) pathways, as well as various inflammatory cytokines, as an indirect means of regulating MYC overexpression in AML. Furthermore, we highlight Food and Drug Administration (FDA)-approved drugs for AML, and the results of preclinical and clinical studies on novel agents that have been or are currently being tested for efficacy and tolerability in AML therapy. Overall, this review summarizes our current knowledge of the molecular processes that promote leukemogenesis, as well as the various agents that intervene in specific pathways and directly or indirectly modulate c-MYC to disrupt AML pathogenesis and drug resistance.

Distribution and antibiotic resistance analysis of Gram positive cocci in bloodstream infections in a hospital in Inner Mongolia

To investigate the strain composition and drug resistance characteristics of G+(Gram positive cocci) cocci causing bloodstream infections in the People's Hospital of Inner Mongolia Autonomous Region in recent years and provide a basis for the empirical and rational use of drugs for the prevention and treatment of bloodstream infections caused by G+cocci. The strain composition and drug-resistant characteristics of G+cocci isolated from positive blood culture specimens sent to various departments of the Inner Mongolia Autonomous Region People's Hospital from January 2015 to December 2022 were retrospectively analyzed, and the higher detection rates of Staphylococcus hominis and Staphylococcus epidermidis, Enterococcus faecium and Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) were examined. MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) were comparatively analyzed for resistance. The resistance data were analyzed by Whonet 5.6 statistical software, the significance of difference was analyzed by SPSS 22.0 software, and the resistance rate was compared by χ2 test. The results showed that 1 209 strains of G+cocci, in terms of the composition ratio, from high to low, were mainly human staphylococci (32.5%,393/1 209), Staphylococcus epidermidis (27.8%, 336/1 209), Staphylococcus aureus (14.9%,180/1 209) and Enterococcus faecalis (10.6%, 128/1 209). Among them, the detection rate of methicillin-resistant Staphylococcus aureus (MRSA) (42.8%, 77/180) was lower than that of methicillin-resistant coagulase-negative staphylococcus (MRCNS) (71.5%, 608/850); and among enterococci, the detection rate of Enterococcus faecalis (71.5%, 128/179) was much higher than that of Enterococcus faecalis (28.5%, 51/179). For drug resistance, the resistance rate to five commonly used antimicrobial drugs, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin and tetracycline, was higher in Staphylococcus hominis than in Staphylococcus epidermidis (χ2=7.152-64.080, P<0.05); however, for the aminoglycoside antimicrobial drug gentamicin, the rate of resistance in Staphylococcus humanus was lower than in Staphylococcus epidermidis, and the difference was statistically significant (χ2=11.895, P<0.05); no strains resistant to linezolid and vancomycin were found in both. Comparison of the resistance rates to seven antimicrobial drugs, gentamicin, rifampicin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin and tetracycline, was significantly higher in MRSA than in MSSA (χ2=6.169-56.941, P<0.05); however, the resistance rate to cotrimoxazole, MRSA (15.6%, 12/77) was significantly lower than that of MSSA (35.3%, 36/102), and the difference was statistically significant (χ2=5.155, P<0.05); MRSA and MSSA resistant to linezolid and vancomycin were not found. The resistance rate of Enterococcus faecalis to penicillin G and ampicillin was much higher than that of Enterococcus faecalis, and the difference was statistically significant (χ2=22.965, P<0.05), and vancomycin-resistant enterococci (VRE) were not found. In conclusion, for staphylococci, except for individual antibiotics, S.hominis and MRSA were more resistant to most antimicrobial drugs than S. epidermidis and MSSA, showing a multidrug-resistant pattern. For enterococci, except for penicillin G and ampicillin resistance rate, Enterococcus faecalis is much higher than Enterococcus faecalis, the rest of the antimicrobial drugs did not see a significant difference, in addition to vancomycin-resistant enterococci were not detected. Clinicians should pay great attention to the monitoring data of multidrug-resistant G+cocci isolated from blood cultures to provide a basis for empirical and rational use of drugs in the clinic, to effectively prevent and reduce the incidence of bloodstream infections caused by G+cocci.

Drug resistance and genetic characteristics of one Eimeria tenella isolate from Xiantao, Hubei Province, China.

Chicken coccidiosis causes retarded growth and low production performance in poultry, resulting in huge economic losses to the poultry industry. In order to prevent and control chicken coccidiosis, great efforts have been made to develop new drugs and vaccines, which require pure isolates of Eimeria spp. In this study, we obtained the Eimeira tenella Xiantao isolate by single oocyst isolation technology and compared its genome with the reference genome GCF_000499545.2_ETH001 of the Houghton strain. The results of the comparative genomic analysis indicated that the genome of this isolate contained 46,888 single nucleotide polymorphisms (SNPs). There were 15,107 small insertion and deletion variations (indels), 1693 structural variations (SV), and 3578 copy number variations (CNV). In addition, 64 broilers were used to determine the resistance profile of Xiantao strain. Drug susceptibility testing revealed that this isolate was completely resistant to monensin, diclazuril, halofuginone, sulfachlorpyrazine sodium, and toltrazuril, but sensitive to decoquinate. These data improve our understanding of drug resistance in avian coccidia.

Distribution and Drug Resistance Characteristics of Pathogenic Bacteria in the Elderly Population in China in 2021

To study the distribution and drug resistance characteristics of pathogenic bacteria in the elderly population of China by collecting and analyzing the standardized case data on the pathogens of infections in elderly patients, and to facilitate the establishment of a standardized layered surveillance system for pathogenic bacteria in China. We collected the case data of elderly patients (≥65 years old) from 62 sentinel hospitals across the country in 2021. Then, we statistically analyzed the data by patient age, their geographical region, the distribution of pathogenic bacteria, and the drug resistance characteristics of main pathogens. A total of 3468 cases from across the country were included in the study. The top three sources of patients were the intensive care unit (13.2%), the department of respiratory medicine (11.2%), and the department of general surgery (8.4%). The top three types of specimens were urine (25.5%), sputum (20.6%), and blood (18.7%). A total of 3468 strains of pathogens were isolated, among which, 78.9% were gram-negative bacteria and 21.1% were gram-positive bacteria. The top five types of bacteria were Escherichia coli (20.9%), Klebsiella pneumoniae (18.3%), Pseudomonas aeruginosa (11.2%), Staphylococcus aureus (9.0%), and Acinetobacter baumannii (7.0%). The isolation rates of common important drug-resistant bacteria were 38.0% for methicillin-resistant Staphylococcus aureus (MRSA), 68.7% for carbapenem-resistant Acinetobacter baumannii (CRAB), and 38.2% for carbapenem-resistant Pseudomonas aeruginosa (CRPA), 20.1% for carbapenem-resistant Klebsiella pneumoniae (CRKP), 5.2% for carbapenem-resistant Escherichia coli (CRECO), and 2.1% for vancomycin-resistant Enterococcus (VRE). There were differences in the isolation rates of CRAB and CRKP in clinical care in the elderly population in seven geographical regions of China (P<0.05). Klebsiella pneumoniae is the most important pathogen in the elderly population ≥85 years old, and the isolation rates of CRKP showed significant differences in different age groups (P<0.05). There are significant differences in the drug resistance of pathogenic bacteria in the elderly populations of different regions and age groups in China. Therefore, monitoring the distribution and drug resistance of pathogenic bacteria in the elderly population and formulating targeted treatment plans according to the characteristics of the specific regions and age groups are of great significance to the improvement in the treatment outcomes and prognosis of the elderly population.

Analysis of epidemiological characteristics of extrapulmonary tuberculosis from South-Central China.

This study aimed to investigate the epidemiological and drug resistance (DR) characteristics of extrapulmonary tuberculosis (EPTB) in South-Central China. EPTB inpatients who were culture-positive for Mycobacterium tuberculosis were retrospectively included in a study at a provincial TB hospital in Hunan, a province in South-Central China, from January 2013 to December 2021. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment records. Descriptive statistical methods and a Chi-squared test were used to analyze the epidemiological and DR characteristics of EPTB patients. A logistic regression model was used to explore the risk factors of rifampicin-resistant/multidrug-resistant (RR/MDR)-EPTB. A total of 1,324 cases were included. The majority of EPTB patients were in the age range of 20-29 years, were predominantly men (male-to-female ratio: 2.03), and were farmers (65.63%). Most EPTB cases were found in 2013 and 2017 from 2013 to 2021. The most prevalent subtypes of EPTB were lymphatic TB (29.83%, 395/1,324), multiple EPTB (20.85%, 276/1,324), and musculoskeletal TB (14.65%, 194/1,324). Musculoskeletal TB and genitourinary TB predominantly presented as exclusive EPTB forms, while lymphatic TB and pharyngeal/laryngeal TB often co-occurred with pulmonary TB (PTB). Drug susceptibility testing results showed that total DR rates (resistance to any of RFP, isoniazid [INH], streptomycin [STR], and/or ethambutol [EMB]) and RR/MDR rates in EPTB were 25.23% and 12.39%, respectively. Musculoskeletal TB exhibited the highest rates of total DR (31.40%), INH resistance (28.90%), STR resistance (20.10%), EMB resistance (6.20%), MDR (13.90%), and poly-DR (6.70%). The multivariable logistic regression model showed that patients aged from 20 to 59 years (compared to those aged 10 years), workers (compared to retirees), and EPTB patients from the south and west of Hunan (compared to those from the east of Hunan) were at an increased risk of developing RR/MDR EPTB (all OR values > 1). Our study provided a detailed account of the epidemiological and DR characteristics of EPTB in Hunan province, China. The significant DR rates, particularly in musculoskeletal TB cases, highlight the need for timely diagnosis, effective drug susceptibility testing, and the development of more effective treatment regimens for EPTB, especially targeting musculoskeletal TB treatments.

Prevalence and antimicrobial susceptibility pattern of Mycobacterium abscessus complex isolates in Chongqing, Southwest China

ObjectivesTo investigate the prevalence of Mycobacterium abscessus complex (MABC), drug resistance characteristics, and the relationship between clarithromycin (CLA) susceptibility and MABC genotype in Chongqing, China. MethodsA total of 434 NTM patient isolates were collected between October 2018 and October 2019. Isolates confirmed to be non-tuberculous mycobacteria (NTM) were tested for minimal inhibitory concentrations of antimicrobial agents. In addition, rrl and erm(41) gene sequences were used to analyze the acquired macrolide resistance and inducible macrolide resistance. ResultsOverall, 17 different NTM species were detected, of which M. abscessus (22.6 %, 91/403) was most prevalent. Amikacin, CLA, azithromycin and cefoxitin exhibited potent activities against MABC organisms, but no significant differences were observed in drug resistance rates between M. abscessus and M. massiliense (P > 0.05). On day 3 of culture, the acquired resistance rate against CLA was 7.4 % (9/121). Of 41 MABC isolates with inducible CLA resistant, 95.1 % (39/41) isolates belonged to the erm(41) T28 sequevar, while the remaining 4.9 % (2/41) possessed the M. massiliense genotype. All erm(41) C28 sequevar isolates were sensitive to CLA on day3 and day 14 of culture. Meanwhile, of the 5 erm(41) T28 isolates with acquired resistance, all possessed rrl 2058/2059 mutations, including 3 isolates with A2058C mutation and 2 isolates with A2059G mutation. While 2 of the 4 M. massiliense isolates with acquired resistance possessed the A2059G mutation, and one isolate possessed the A2058G mutation. ConclusionErm(41) and rrl gene could serve as useful markers for predicting macrolide susceptibility of MABC complex isolates.

Immunological and molecular assessment of HIV-1 mutations for antiretroviral drug resistance in Saudi Arabia.

Human Immunodeficiency Virus (HIV) is a significant threat to public health. HIV genotyping and antiretroviral resistance testing may have contributed to improved non-treated management. Immune markers might assist HIV-1 diagnosis and drug-resistant variant identification. HIV-1 immunogenicity and molecular characteristics of antiretroviral drug resistance are evaluated in 56 treatment-naive HIV patients. DNA sequencing and retroviral resistance testing identified HIV-1 genotypes. 55.4% of patients were susceptible to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) antiretroviral drugs, whereas 44.6% had drug-resistance mutations against at least one antiretroviral drug. 3.6% of cases had PI-resistant mutations, while 30.4% had NRTI-resistant mutations, and 30.4% had NNRTI-resistant mutations. In patients who are susceptible to PI, the mean value of human plasma sCD80 is 2.11 ± 0.65 ng/mL; in patients with mutations, it is 3.93 ± 2.91 ng/mL. Individuals who are susceptible to PI have plasma sCD27 levels of 78.7 ± 63.2 U/mL, whereas individuals who are mutant have levels of 56.5 ± 32.1 U/mL. IP-10's mean value was 363 ± 109.2 pg/mL for the susceptible patients and 429 ± 20.7 pg/mL for the mutated patients. In susceptible patients, the plasma sCD4 level is 0.163 ± 0.229 ng/mL; in mutant patients, it is 0.084 ± 0.012 ng/mL. The data showed a relative relation between immunological parameters such as sCD80, sCD27, sCD4, and IP-10 and mutation for drug resistance.

Antimicrobial resistance and genome characteristics of Salmonella enteritidis from Huzhou, China.

Salmonella enteritidis is a main pathogen responsible for sporadic outbreaks of gastroenteritis, and therefore is an important public health problem. This study investigated the drug resistance and genomic characteristics of S. enteritidis isolated from clinical and food sources in Huzhou, Zhejiang Province, China, from February 1, 2021, to December 30, 2023. In total, 43 S. enteritidis strains isolated during the study period were subjected to virulence gene, drug resistance gene, genetic correlation, antibiotic resistance, and multilocus sequence typing analyses. All 43 isolates were identified as ST11, and contained 108 virulence-related genes. Drug sensitivity analysis of the 43 isolates showed resistance rates of 100% to nalidixic acid and 90.70% to ampicillin and ampicillin/sulbactam. Multidrug resistance is a serious issue, with 81.40% of strains resistant to three or more antibacterial drugs. Genome sequencing indicated that S. enteritidis possessed 23 drug resistance genes, of which 14 were common to all 43 isolates. Phylogenetic analysis based on core genome single-nucleotide polymorphisms divided the 43 S. enteritidis strains into three clusters, with the 10 samples from an outbreak forming an independent branch located in cluster 3.

Analysis of Drug Resistance Characteristics of Mycobacterium Tuberculosis in Anhui Province, 2016-2022.

To preliminarily assess the prevalence and control effect of tuberculosis and drug-resistant tuberculosis (TB) in Anhui province, and analyze the trends in the changing drug resistance spectrum of Mycobacterium tuberculosis (Mtb) isolated in Anhui province from 2016 to 2022. From 2016 to 2022, a total of 2336 culture-positive tuberculosis strains were collected from four drug resistance monitoring sites. Patient demographic information was collected and drug susceptibility testing was conducted. Among the 2336 Mycobacterium tuberculosis complex strains, 1788 (76.54%) were from male patients and 548 (23.46%) were from female patients. The majority were of Han ethnicity, from rural areas, and employed in agriculture, with 12.54% (285/2273) having diabetes. A total of 1893 (81.04%) strains were sensitive to all six anti-TB drugs tested, and 443 (18.96%) strains were resistant to at least one or more anti-TB drugs. The drug resistance rate for patients undergoing initial treatment was 16.80% (348/2071), and 35.85% (95/265) for those receiving retreatment. Among the six anti-TB drugs, the resistance rates from highest to lowest were: INH (10.55%, 236/2336), SM (8.18%, 183/2336), OFX (6.53%, 146/2336), RFP (5.95%, 133/2336), EMB (2.37%, 53/2336), KM (1.97%, 44/2336). Significant differences were observed in MDR strains across different ages, types, with or without diabetes, and geographical sources (χ2=14.895,76.534,6.032,5.109, all P<0.05). The tuberculosis prevention and control measures have controlled the drug resistance rate of Mycobacterium tuberculosis to a certain extent. However, there are still statistical differences in drug resistance rates among TB patients with different categories, age groups, regions, and diabetic diseases. Early detection and prompt treatment of patients with drug-resistant TB remain critical to controlling the spread of this disease.

Characteristics of drug resistance and biofilm formation in carbapenem-resistant Acinetobacter baumannii in hospitalized children

To study the distribution, drug resistance, and biofilm characteristics of carbapenem-resistant Acinetobacter baumannii (CRAB) isolated from hospitalized children, providing a reference for the prevention and treatment of CRAB infections in hospitalized children. Forty-eight CRAB strains isolated from January 2019 to December 2022 were classified into epidemic and sporadic strains using repetitive extragenic palindromic sequence-based polymerase chain reaction. The drug resistance, biofilm phenotypes, and gene carriage of these two types of strains were compared. Both the 22 epidemic strains and the 26 sporadic strains were producers of Class D carbapenemases or extended-spectrum β-lactamases with downregulated outer membrane porins, harboring the VIM, OXA-23, and OXA-51 genes. The biofilm formation capability of the sporadic strains was stronger than that of the epidemic strains (P<0.05). Genes related to biofilm formation, including Bap, bfs, OmpA, CsuE, and intI1, were detected in both epidemic and sporadic strains, with a higher detection rate of the intI1 gene in epidemic strains (P<0.05). CRAB strains are colonized in the hospital, with sporadic strains having a stronger ability to form biofilms, suggesting the potential for forming new clonal transmissions in the hospital. Continuous monitoring of the epidemic trends of CRAB and early warning of the distribution of epidemic strains are necessary to reduce the risk of CRAB infections in hospitalized children.

Abstract LB260: Overexpression of ABCC1 and ABCG2 confers resistance to talazoparib, a poly polymerase inhibitor

Abstract Aims: The overexpression of ABC transporters on cancer cell membranes is one of the most common causes of multidrug resistance (MDR). This study investigates the impact of ABCC1 and ABCG2 on the resistance to talazoparib (BMN-673), a potent poly (ADP-ribose) polymerase (PARP) inhibitor, in ovarian cancer treatment. Methods: The cell viability test was used to indicate the effect of talazoparib in different cell lines. Computational molecular docking analysis was conducted to simulate the interaction between talazoparib and ABCC1 or ABCG2. The mechanism of talazoparib resistance was investigated by constructing talazoparib-resistant subline A2780/T4 from A2780 through drug selection with gradually increasing talazoparib concentration. Results: Talazoparib cytotoxicity decreased in drug-selected or gene-transfected cell lines overexpressing ABCC1 or ABCG2 but can be restored by ABCC1 or ABCG2 inhibitors. Talazoparib competitively inhibited substrate drug efflux activity of ABCC1 or ABCG2. Upregulated ABCC1 and ABCG2 protein expression on the plasma membrane of A2780/T4 cells enhances resistance to other substrate drugs, which could be overcome by the knockout of either gene. In vivo experiments confirmed the retention of drug-resistant characteristics in tumor xenograft mouse models. Conclusions: The therapeutic efficacy of talazoparib in cancer may be compromised by its susceptibility to MDR, which is attributed to its interactions with the ABCC1 or ABCG2 transporters. The overexpression of these transporters can potentially diminish the therapeutic impact of talazoparib in cancer treatment. Citation Format: Shuo Fang, Xiaona Fang. Overexpression of ABCC1 and ABCG2 confers resistance to talazoparib, a poly polymerase inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB260.

Phenotypic Characteristics, Antimicrobial Susceptibility and Virulence Genotype Features of Trueperella pyogenes Associated with Endometritis of Dairy Cows.

Trueperella pyogenes can cause various infections in the organs and tissues of different livestock (including pigs, cows, goats, and sheep), including mastitis, endometritis, pneumonia, or abscesses. Moreover, diseases induced by T. pyogenes cause significant economic losses in animal husbandry. In recent large-scale investigations, T. pyogenes has been identified as one of the main pathogens causing endometritis in lactating cows. However, the main treatment for the above-mentioned diseases is still currently antibiotic therapy. Understanding the impact of endometritis associated with T. pyogenes on the fertility of cows can help optimize antibiotic treatment for uterine diseases, thereby strategically concentrating the use of antimicrobials on the most severe cases. Therefore, it is particularly important to continuously monitor the prevalence of T. pyogenes and test its drug resistance. This study compared the uterine microbiota of healthy cows and endometritis cows in different cattle farms, investigated the prevalence of T. pyogenes, evaluated the genetic characteristics and population structure of isolated strains, and determined the virulence genes and drug resistance characteristics of T. pyogenes. An amount of 186 dairy cows were involved in this study and 23 T. pyogenes strains were isolated and identified from the uterine lavage fluid of dairy cows with or without endometritis.

Whole Genome Sequence-Based Analyses of Drug Resistance Characteristics, Genetic Diversity, and Transmission Dynamics of Drug-Resistant Mycobacterium tuberculosis in Urumqi City.

This study aims to analyze the drug resistance spectrum, genetic diversity, and transmission dynamics to provide a basis for the prevention and control of drug-resistant (DR) tuberculosis (TB) epidemics. This retrospective study is based on routine national drug resistance surveillance. The demographic, epidemiological, and clinical information on DR-TB patients from 2016 to 2021 was collected and used for phenotypic drug susceptibility testing and whole-genome sequencing. It was indicated that L2.2.1 was the dominant lineage in Urumqi. The drug resistance spectrum in Urumqi was narrow, which means more drug combinations can be used for clinical treatment. Furthermore, mutations identification of drug-resistance gene katG, rpoB, embA/B, rrs, rpsL, eis, gyrA/B, folC and tryA are important for clinical drug use. However, mutations in cross-resistance genes rrs have limited guidance for clinical selection of KM, CPM and AK. Moreover, there is an increased risk of cluster transmission of DR-TB, and the difference in clustering rate among L2, L3, and L4 was not statistically significant (χ2 = 2.6410, p = 0.2670). In the Urumqi, DR-TB has a complex prevalence state, a narrow drug resistance spectrum, and a high clustering rate and burden of drug resistance. To reduce the burden of DR-TB, related research should be strengthened, and the development of prevention, control, and treatment strategies should be accelerated.

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

ObjectiveChina is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. MethodsA population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. ResultsA total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023–1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. ConclusionOur results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Metagenome-Based Analysis of the Microbial Community Structure and Drug-Resistance Characteristics of Livestock Feces in Anhui Province, China.

We analyzed metagenome data of feces from sows at different physiological periods reared on large-scale farms in Anhui Province, China, to provide a better understanding of the microbial diversity of the sow intestinal microbiome and the structure of antibiotic-resistance genes (ARGs) and virulence genes it carries. Species annotation of the metagenome showed that in the porcine intestinal microbiome, bacteria were dominant, representing >97% of the microorganisms at each physiological period. Firmicutes and Proteobacteria dominated the bacterial community. In the porcine gut microbiome, the viral component accounted for an average of 0.65%, and the species annotation results indicated that most viruses were phages. In addition, we analyzed the microbiome for ARGs and virulence genes. Multidrug-like, MLS-like, and tetracycline-like ARGs were most abundant in all samples. Evaluation of the resistance mechanisms indicated that antibiotic inactivation was the main mechanism of action in the samples. It is noteworthy that there was a significant positive correlation between ARGs and the total microbiome. Moreover, comparative analysis with the Virulence Factor Database showed that adhesion virulence factors were most abundant.

Novel Antimicrobial Approaches to Combat Bacterial Biofilms Associated with Urinary Tract Infections.

Urinary tract infections (UTIs) are prevalent bacterial infections in both community and healthcare settings. They account for approximately 40% of all bacterial infections and require around 15% of all antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs for several decades, the significant increase in antibiotic resistance in recent years has made many previously effective treatments ineffective. Biofilm on medical equipment in healthcare settings creates a reservoir of pathogens that can easily be transmitted to patients. Urinary catheter infections are frequently observed in hospitals and are caused by microbes that form a biofilm after a catheter is inserted into the bladder. Managing infections caused by biofilms is challenging due to the emergence of antibiotic resistance. Biofilms enable pathogens to evade the host's innate immune defences, resulting in long-term persistence. The incidence of sepsis caused by UTIs that have spread to the bloodstream is increasing, and drug-resistant infections may be even more prevalent. While the availability of upcoming tests to identify the bacterial cause of infection and its resistance spectrum is critical, it alone will not solve the problem; innovative treatment approaches are also needed. This review analyses the main characteristics of biofilm formation and drug resistance in recurrent uropathogen-induced UTIs. The importance of innovative and alternative therapies for combatting biofilm-caused UTI is emphasised.

The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer.

Metal ions exert pivotal functions within the human body, encompassing essential roles in upholding cell structure, gene expression regulation, and catalytic enzyme activity. Additionally, they significantly influence various pathways implicated in divergent mechanisms of cell death. Among the prevailing malignant tumors of the digestive tract worldwide, gastric cancer stands prominent, exhibiting persistent high mortality rates. A compelling body of evidence reveals conspicuous ion irregularities in tumor tissues, encompassing gastric cancer. Notably, metal ions have been observed to elicit distinct contributions to the progression, drug resistance, and biological attributes of gastric cancer. This review consolidates pertinent literature on the involvement of metal ions in the etiology and advancement of gastric cancer. Particular attention is directed towards metal ions, namely, Na, K, Mg, Ca, Fe, Cu, Zn, and Mn, elucidating their roles in the initiation and progression of gastric cancer, cellular demise processes, drug resistance phenomena, and therapeutic approaches.

The Recent Transmission and Associated Risk Factor of Mycobacterium tuberculosis in Golmud City, China.

Tuberculosis (TB) remains a severe public health problem globally, and it is essential to comprehend the transmission pattern to control tuberculosis. Herein, we evaluated the drug-resistant characteristics, recent transmission, and associated risk factors of TB in Golmud, Qinghai, China. In this study, we performed a population-based study of patients diagnosed with TB in Golmud from 2013 to 2018. Drug-susceptibility testing and whole-genome sequencing were performed on 133 Mycobacterium tuberculosis strains. The genomic clustering rate was calculated to evaluate the level of recent transmission. Risk factors were identified by logistic regression analysis. Our results showed that 46.97% (62/132) of strains were phylogenetically clustered and formed into 23 transmission clusters, suggesting a high recent transmission of TB in the area. 12.78% (17/133) strains were multidrug-resistant/rifampicin tuberculosis (MDR/RR-TB), with a high drug-resistant burden. Based on drug resistance gene analysis, we found 23 strains belonging to genotype MDR/RR-TB, where some strains may have borderline mutations. Among these strains, 65.2% (15/23) were found within putative transmission clusters. Additionally, risk factor analysis showed that recent transmission of TB happened more in patients with Tibetan nationality or older age. Overall our study indicates that the recent transmissions of MTB strains, especially genotypic MDR/RR strains, drive the tuberculosis epidemic in Golmud, which could contribute to developing effective TB prevention and control strategies.