Mammalian intestine contains a large diversity of commensal microbiota, which is far more than the number of host cells. Probiotics play an insecure and protective role against the colonization of intestinal pathogenic microbes and increase mucosal integrity by stimulating epithelial cells. Probiotics have innate capabilities in many ways, including receptor antagonism, receptor expression, binding and expression of adapter proteins, expression of negative regulatory signal molecules, induction of microRNAs, endotoxin tolerance, and ultimately secretion of immunomodulatory proteins, lipids, and metabolites to modulate the immune system. Probiotic bacteria can affect homeostasis, inflammation, and immunopathology through direct or indirect effects on signaling pathways as immunosuppressant or activators. Probiotics suppress inflammation by inhibiting various signaling pathways such as the nuclear factor‐κB (NF‐κβ) pathway, possibly related to alterations in mitogen‐activated protein kinases and pattern recognition receptors pathways. Probiotics can also inhibit the binding of lipopolysaccharides to the CD14 receptor, thereby reducing the overall activation of NF‐κβ and producing proinflammatory cytokines. Some effects of modulation by probiotics include cytokine production by epithelial cells, increased mucin secretion, increased activity of phagocytosis, and activation of T and natural killer T cells, stimulation of immunoglobulin A production and decreased T cell proliferation. Intestinal microbiota has a major impact on the systemic immune system. Specific microbiota controls the differentiation of cells in lamina propria, in which Th17 cells secrete interleukin 17. The presence of Th17 and Treg cells in the small intestine is associated with intestinal microbiota, with the preferential Treg differentiation and the absence of Th17 cells, possibly reflecting alterations in the lamina propria cytokines and the intestinal gut microbiota.

Background: Klebsiella pneumoniae is a public health concern because of its ability to develop multidrug resistance and hypervirulent genotypes, of those capsular types K1 and K2 cause community and nosocomial life-threatening infections. This study aimed to determine the antibiotic susceptibility patterns and genotypic traits of a collection of Klebsiella spp. isolates. Furthermore, the clonal relatedness of bla NDM producing strains was investigated. Methods: During a 19-months surveillance study, 122 Klebsiella spp. isolates were cultured from extraintestinal specimens of patients admitted to the tertiary referral hospital in Semnan, Iran. Isolates were identified using biochemical tests and subjected to determination of phylogroups, capsular types and virulence/resistance genes content. Hypervirulent K. pneumoniae (hvKp) strains were detected genotypically, and Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR fingerprinting was used to determine the clonality of bla NDM producing strains. Results: Multidrug resistant phenotype was detected in 75 (61.5%) isolates and amikacin was found as the most potent antibiotic with the susceptibility rate of 85.2%. The carbapenemase genes were detected in 45 (36.8%) strains, including 21 (17.2%) bla OXA-48 , 7 (5.6%) bla NDM-1 , 14 (11.4%) bla NDM-1/OXA-48 and 3 (2.4%) bla IMP-carrying strains, while 55 (45.08%) isolates showed carbapenem resistant phenotype. The first bla NDM-1 carrying strain was cultured from a sputum specimen on March 2015, while the last positive one was recovered from blood culture on September 2016. Most of the isolates (80.3%) belonged to phylogroup I, and bla NDM-1 was identified among all three phylogroups. The ERIC-PCR clustered the 101 bla NDM negative and 21 bla NDM-1 positive isolates into 25 and five clusters, respectively, and the latter group belonged to clonal complex 147 (CC147). One K1 and 15 K2 bla NDM-1 negative isolates were detected, of those three strains were identified as hvKp. Five K2 positive strains, including four bla OXA-48 producer and one hvKp sequence type 86 (ST86) were carbapenem resistant. Among carbapenem resistant isolates, CC147 strains harboured higher rates of siderophores iutA and ybtS.

Background The Escherichia coli sequence type 131 (ST131) is a well established clone causing significant extraintestinal infections worldwide. However, no studies have been reported the phenotypic and molecular traits of ST131 isolates in comparison to other clones of E. coli from Iran. So, we determined the differences between 69 ST131 strains collected during a one year surveillance study and 84 non-ST131 isolates, including 56 clinical fluoroquinolone resistant and 28 broiler colibacillosis isolates in terms of clonality and genetic background. Results ST131 isolates were associated with phylogroup B2 (68 out of 69 isolates, 98.4%), while clinical non-ST131 and fluoroquinolone resistant broiler isolates mainly belonged to phylogroup A. The highest virulence score was observed in ST131 clone, while they showed less diversity in virulence profiles than other clinical isolates. Almost all of the ST131 isolates (95.6%) were ExPEC and had the highest virulence scores, but their resistance scores were less than clinical non-ST131 isolates. Broiler isolates showed higher prevalence of ExPEC-associated virulence genes and CTX-M-G1/G9 resistance determinants as compared to clinical non-ST131 isolates. While bla OXA-48/NDM carbapenemases were mostly found in ST131 clone, resistance rate against ertapenem was higher among clinical non-ST131 strains. According to ERIC-based fingerprinting, the ST131 strains were more genetically similar, followed by non-ST131 and broiler isolates. Conclusions ST131 isolates possess the ability to make a balance between clonality and extent of resistance/virulence genes content, so this phenomenon gives a fitness advantage over other E. coli clones. The broilers E. coli population poses a potential zoonotic risk which could be transmitted to the community through the food chain. A number of factors are involved in the dissemination of and infections due to ST131 clone.

Recent studies demonstrated that a combination of the gut microbiome has the vital effect on the efficacy of anticancer immune therapies. Regulatory effects of microbiota have been shown in different types of cancer therapies such as chemotherapy and immunotherapy. Immune‐checkpoint‐blocked therapies are the recent efficient cancer immunotherapy strategies. The target of immune‐checkpoint blocking is cytotoxic T lymphocyte protein‐4 (CTLA‐4) or blockade of programmed death‐1 (PD‐1) protein and its ligand programmed death ligand 1 (PD‐L1) that they have been considered as cancer immunotherapy in recent years. In the latest studies, it have been demonstrated that several gut bacteria such as Akkermansia muciniphila, Bifidobacterium spp., Faecalibacterium spp., and Bacteroides fragilis have the regulatory effects on PD‐1, PD‐L1, and CTLA‐4 blocked anticancer therapy outcome.

Objectives Escherichia coli sequence types (STs) 69, 73, 95, 127, and 131 are major STs frequently causing extraintestinal infections. The prevalence of specific clones and their virulence and resistance profiles has not been described from Iran. The aim of this study was to characterize antimicrobial-susceptibility profiles and virulence traits of five major clones of E. coli recovered from human extraintestinal infections in Semnan, Iran. We compared these traits between major ST clones and also between O25b and O16 subgroups of the ST131 clone. Methods We characterized the five major ST clones among 335 collected E. coli isolates obtained from extraintestinal infections, and phylogenetic groups, antimicrobial susceptibility, and virulence/resistance-gene profiles of these major STs were studied. Results The highest rates of the multidrug-resistance phenotype were detected among ST131 (85.7%) and ST69 (41.7%), and trimethoprim/sulfamethoxazole resistance was detected significantly among the latter clone. Of the 151 isolates belonging to major ST clones, bla OXA-48 was detected among all except the ST127 clone, while bla NDM genes were harbored by 14 (9.2%) isolates, which all belonged to the ST131 clone. Aggregate virulence scores (median) of ST131 isolates (11) were slightly higher than ST69 (8.50) strains, but were lower than ST73 (16), ST95 (16), and ST127 (12.50) isolates. Principal-coordinate analysis revealed distinct virulence profiles with the ST131 clone. ST73, ST95 and ST131 were enriched with “urovirulence” traits, including phylogroup B2 and group B2-associated accessory traits ( chuA , iutA , yfcV , papGII , usp , kpsMTII and malX ) and the derived variables extraintestinal pathogenic E. coli and uropathogenic E. coli . In contrast, ST69 was depleted of these traits, but enriched with phylogroups D and E. Conclusion Our data emphasize that isolates of the ST131 clone have the ability to make a balance between resistance and virulence traits to establish a wider clone in extraintestinal pathogenic E. coli .

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Escherichia coli sequence type 131 (ST131) is a globally dominant multidrug-resistant clone that is commonly associated with extraintestinal infections. Specific sublineages have been shown to have emerged and spread within ST131, highlighting the complex nature of ST131 epidemiology.

Background: Bloodstream infections are considered a significant medical concern associated with high morbidity and mortality rates. Therefore, physicians should be guided to use antimicrobial susceptibility patterns in order to select appropriate empiric antimicrobial agents to treat the patients who suffer from bacteremia. Objective: The present study aimed to determine antimicrobial resistance and susceptibility patterns in isolates collected from bloodstream infections. Materials and Methods: To achieve this, a total of 710 bacterial blood culture isolates were collected from Sina hospital, and then susceptibility patterns to a number of antibiotics were analyzed according to Clinical and Laboratory Standards Institute guidelines. Results: The identified isolates included Staphylococcus aureus 14 (20.6%), Escherichia coli 14 (20.6%), Acinetobacter baumannii 12 (17.6%), Pseudomonas aeruginosa 11 (16.2%), Coagulasenegative Staphylococcus 8 (11.8%), Klebsiella pneumoniae 6 (8.8%), and Enterobacter spp. 3 (4.4%). The total resistance rate to co-trimoxazole, ceftriaxone, ceftazidime, cefotaxime, ofloxacin, gentamicin, ciprofloxacin, levofloxacin, amikacin, and imipenem was 44 (64.7%), 42 (61.8%), 39 (57.4%), 38 (55.9%), 35 (51.51%), 32 (47.1%), 31 (45.6%), 25 (36.8%), and 27 (39.7%), respectively. Finally, the susceptibility rate to amikacin and imipenem was 43 (63.2%) and 41 (60.3%), respectively. Conclusion: In general, A. baumannii strains isolated from blood cultures were resistant to most antibiotics and the greatest sensitivity was observed to gentamicin (58.3%) compared to other antibiotics. Therefore, gentamicin was found as the most effective antibiotic for treating bloodstream infections caused by A. baumannii.