Introduction: Factors other than PD-L1 (Programmed Death Ligand 1) are being sought as predictors for cancer immuno- or chemoimmunotherapy in ongoing studies and long-term observations. Despite high PD-L1 expression on tumor cells, some patients do not benefit from immunotherapy, while others, without the expression of this molecule, respond to immunotherapy. Attention has been paid to the composition of the gut microbiome as a potential predictive factor for immunotherapy effectiveness. Materials and Methods: Our study enrolled 47 Caucasian patients with stage IIIB or IV non-small cell lung cancer (NSCLC). They were eligible for treatment with first- or second-line immunotherapy or chemoimmunotherapy. We collected stool samples before the administration of immunotherapy. We performed next-generation sequencing (NGS) on DNA isolated from the stool sample and analyzed bacterial V3 and V4 of the 16S rRNA gene. Results: We found that bacteria from the families Barnesiellaceae, Ruminococcaceae, Tannerellaceae, and Clostridiaceae could modulate immunotherapy effectiveness. A high abundance of Bacteroidaaceae, Barnesiellaceae, and Tannerellaceae could extend progression-free survival (PFS). Moreover, the risk of death was significantly higher in patients with a high content of Ruminococcaceae family (HR = 6.3, 95% CI: 2.6 to 15.3, p < 0.0001) and in patients with a low abundance of Clostridia UCG-014 (HR = 3.8, 95% CI: 1.5 to 9.8, p = 0.005) regardless of the immunotherapy line. Conclusions: The Clostridia class in gut microbiota could affect the effectiveness of immunotherapy, as well as the length of survival of NSCLC patients who received this method of treatment.
Avian influenza virus (AIV) is a highly diverse and widespread poultry pathogen. Its evolution and adaptation may be affected by multiple host and ecological factors, which are still poorly understood. In the present study, a turkey-origin H9N2 AIV was used as a model to investigate the within-host diversity of the virus in turkeys, quail and ducks in conjunction with the clinical course, shedding and seroconversion. Ten birds were inoculated oculonasally with a dose of 106 EID50 of the virus and monitored for 14 days. Virus shedding, transmission and seroconversion were evaluated, and swabs collected at selected time-points were characterized in deep sequencing to assess virus diversity. In general, the virus showed low pathogenicity for the examined bird species, but differences in shedding patterns, seroconversion and clinical outcome were noted. The highest heterogeneity of the virus population as measured by the number of single nucleotide polymorphisms and Shannon entropy was found in oropharyngeal swabs from quail, followed by turkeys and ducks. This suggests a strong bottleneck was imposed on the virus during replication in ducks, which can be explained by its poor adaptation and stronger selection pressure in waterfowl. The high within-host virus diversity in quail with high level of respiratory shedding and asymptomatic course of infection may contribute to our understanding of the role of quail as an intermediate host for adaptation of AIV to other species of poultry. In contrast, low virus complexity was observed in cloacal swabs, mainly from turkeys, showing that the within-host diversity may vary between different replication sites. Consequences of these observations on the virus evolution and adaptation require further investigation.
Background: The newest method of treatment for patients with NSCLC (non-small cell lung cancer) is immunotherapy directed at the immune checkpoints PD-1 (Programmed Cell Death 1) and PD-L1 (Programmed Cell Death Ligand 1). PD-L1 is the only validated predictor factor for immunotherapy efficacy, but it is imperfect. Some patients do not benefit from immunotherapy and may develop primary or secondary resistance. This study aimed to assess the intestinal resistome composition of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors in the context of clinical features and potentially new prediction factors for assessing immunotherapy efficacy.Methods: The study included 30 advanced NSCLC patients, 19 (57%) men and 11 (33%) women treated with first- or second-line immunotherapy (nivolumab, pembrolizumab or atezolizumab). We evaluated the patient’s gut resistome composition using the high sensitivity of targeted metagenomics.Results: Studies have shown that resistome richness is associated with clinical and demographic factors of NSCLC patients treated with immunotherapy. Smoking seems to be associated with an increased abundance of macrolides, lincosamides, streptogramins and vancomycin core resistome. The resistome of patients with progression disease appears to be more abundant and diverse, with significantly higher levels of genomic markers of resistance to lincosamides (lnuC). The resistance genes lnuC, msrD, ermG, aph(6), fosA were correlated with progression-free survival or/and overall survival, thus may be considered as factors potentially impacting the disease.Conclusion: The results indicate that the intestinal resistome of NSCLC patients with immune checkpoint inhibitors treatment differs depending on the response to immunotherapy, with several distinguished markers. Since it might impact treatment efficacy, it must be examined more deeply.
20 April 2023 in Journal of Global Antimicrobial Resistance
Monophasic Salmonella Typhimurium (1,4,[5],12:i:-) is one of the leading Salmonella serovars causing human salmonellosis in Europe. It has been observed in Poland since 2008. This serovar is considered the one with the highest rate of mcr prevalence. This report presents a sequence characteristic of the multidrug-resistant (MDR) monophasic S. Typhimurium isolated from a pig faecal sample with the confirmed presence of the mcr-1.1 gene. The genome was assembled into the complete chromosome and 4 plasmids: IncHI2 (232 119 bp), IncFIB/IncFIC (133 901 bp), ColRNAI (6659 bp), and Col8282 (4066bp). The strain identified as ST34 carried multiple antimicrobial resistance genes located both on chromosome (tet(B)) and plasmids: mcr-1.1 and blaTEM-1B on ST4-IncHI2, and mef(B), blaTEM-1B, aadA1, qacL, dfrA12, aadA2, cmlA1, sul3, tet(M) on IncFIB/FIC. The mcr-1.1 gene was previously identified in E. coli deriving mainly from poultry, but this is the first case of the occurrence of mcr-positive Salmonella in Poland. The obtained results of analysis of the genome content draw attention to the problem of multidrug-resistant pathogens, especially in the context of resistance to colistin which is a last-resort antimicrobial.
Salmonella Mbandaka is one of the most globally widespread serovars, occurring in many sources and included among twenty serovars that contribute to human salmonellosis in Europe. In Poland, it has been noted in non-human sources since 1996, being found firstly in feeds and later in waterfowl and chicken. Over the years, it gained epidemiological importance, being isolated from a wide range of animal species, including livestock. Generally, it is characterized by sensitivity to most antimicrobials and the ability to form biofilms. The occurrence of cephalosporin-resistant Salmonella in non-human sources is an extremely rare phenomenon in Poland. In this report, we characterized the full genome of the ESBL-producing S. Mbandaka strain isolated from a broiler farm environment (boot swab sample) in Poland in 2022. The isolate was serotyped as S. Mbandaka according to the White–Kaufmann–Le Minor scheme. Antimicrobial susceptibility testing performed with the microbroth dilution method showed its resistance to ampicillin, cefotaxime, ceftazidime, ciprofloxacin, and nalidixic acid. The whole-genome sequence was reconstructed using short and long reads and assembled into the complete chromosome and three plasmids: IncI1 pST113 (89,439 bp), Col(pHAD28) (2699 bp), and Col440 (2495 bp). The strain belonged to sequence type ST413. Plasmid analysis showed blaCTX-M-8 mobilization on IncI1(alpha) surrounded with insertion sequences. The analyzed genome content draws attention to the possibility of the horizontal spread of the resistance genes. To the best of our knowledge, this is the first report of blaCTX-M-8-positive Salmonella in Poland.
Contaminations with cephalosporin-resistant Escherichia coli across the food chain may pose a significant threat to public health because those antimicrobials are critically important in human medicine. The impact of the presented data is especially significant concerning Poland’s role as one of the leading food producers in the EU. This work aimed to characterize the genomic contents of cephalosporin-resistant Escherichia coli (n = 36) isolated from retail meat to expand the official AMR monitoring reported by EFSA. The ESBL mechanism was predominant (via blaCTX-M-1 and blaSHV-12), with the AmpC-type represented by the blaCMY-2 variant. The strains harbored multiple resistance genes, mainly conferring resistance to aminoglycosides, sulfonamides, trimethoprim, tetracyclines. In some isolates, virulence factors—including intimin (eae) and its receptor (tir) were detected, indicating significant pathogenic potential. Resistance genes showed a link with IncI1 and IncB/O/K/Z plasmids. Cephalosporinases were particularly linked to ISEc9/ISEc1 (blaCTX-M-1 and blaCMY-2). The association of virulence with mobile elements was less common—mostly with IncF plasmids. The analysis of E. coli isolated from retail meat indicates accumulation of ARGs and their association with various mobile genetic elements, thus increasing the potential for the transmission of resistance across the food chain.