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Background and Objectives: TB infection is one of the most challengeable epidemiological issues. Complex interactions between microbiota and TB infection have been demonstrated. Alteration in microbial population during TB infection may act as a useful biomarker. The present study examined the microbiota patterns of blood and sputum samples collected from Afghan immigrants and Iranian patients with active TB. Materials and Methods: Sixty active pulmonary TB patients were enrolled in the study. Blood and sputum samples were collected. To detect phylum bacterial composition in the blood and sputum samples, bacterial 16S rRNA quantification by Real-Time qPCR was performed. Results: A significant decrease in Bacteroidetes in Iranian sputum and blood samples of Afghan immigrants and Iranian TB active subjects were seen. While, sputum samples of Afghan immigrants showed no significant differences in Bacteroidetes abundance among TB active and control. Firmicutes were also presented no significant difference between sputum samples of the two races. Actinobacteria showed a significant increase in Iranian and Afghan sputum samples while this phylum showed no significant abundance in Iranian and Afghan TB positive blood samples. Proteobacteria also showed an increase in sputum and blood samples of the two races. Conclusion: An imbalance in Bacteroidetes and Firmicutes abundance may cause an alteration in the microbiota composition, resulting in dysregulated immune responses and resulting in the augmentation of opportunistic pathogens during TB infection, notably Proteobacteria and Actinobacteria. Evaluation of human microbiota under different conditions of TB infection can be critical to a deeper understanding of the disease control.

Abstract Background Clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes could be influenced by genetic polymorphisms in angiotensin I-converting enzyme (ACE1) and ACE2. This study aims to examine three polymorphisms (rs1978124, rs2285666, and rs2074192) on the ACE2 gene and ACE1 rs1799752 (I/D) in patients who have coronavirus disease 2019 (COVID-19) with various SARS-CoV-2 variants. Methods Based on polymerase chain reaction-based genotyping, four polymorphisms in the ACE1 and ACE2 genes have been identified in 2023 deceased patients and 2307 recovered patients. Results The ACE2 rs2074192 TT genotype was associated with the COVID-19 mortality in all three variants, whereas the CT genotype was associated with the Omicron BA.5 and Delta variants. ACE2 rs1978124 TC genotypes were related to COVID-19 mortality in the Omicron BA.5 and Alpha variants, but TT genotypes were related to COVID-19 mortality in the Delta variant. It was found that ACE2 rs2285666 CC genotypes were associated with COVID-19 mortality in Delta and Alpha variants, and CT genotypes in Delta variants. There was an association between ACE1 rs1799752 DD and ID genotypes in the Delta variant and COVID-19 mortality, whereas there was no association in the Alpha or Omicron BA.5 variants. In all variants of SARS-CoV-2, CDCT and TDCT haplotypes were more common. In Omicron BA.5 and Delta, CDCC and TDCC haplotypes were linked with COVID-19 mortality. In addition to COVID-19 mortality, the CICT, TICT, and TICC were significantly correlated. Conclusion The ACE1/ACE2 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To confirm these results, however, more research needs to be conducted.

Abstract It is a growing problem around the world to deal with nontuberculous mycobacteria infection (NTM), but its clinical significance is still largely unknown. This study aims to investigate the epidemiology of NTM infections from various clinical samples and determine their clinical significance. From December 2020 to December 2021, 6125 clinical samples were collected. In addition to phenotypic detection, genotypic detection through multilocus sequence typing (hsp65, rpoB, and 16S rDNA genes) and sequencing was also conducted. Records of patients were consulted for clinical information, such as symptoms and radiological findings. Of the 6,125 patients, 351 (5.7%) were positive for acid-fast bacteria (AFB). Out of 351 AFB, 289 (82.3%) and 62 (17.7%) subjects were identified as M. tuberculosis complex (MTC) and NTM strains, respectively. Isolates of Mycobacterium simiae and M. fortuitum were the most frequent, followed by isolates of M. kansasii and M. marinum. We also isolated M. chelonae, M. canariasense, and M. jacuzzii, which are rarely reported. Symptoms (P = 0.048), radiographic findings (P = 0.013), and gender (P = 0.039) were associated with NTM isolates. M. Fortuitum, M. simiae, and M. kansasii presented with bronchiectasis, infiltration, and cavitary lesions most frequently, while cough was the most common symptom. In conclusion, Mycobacterium simiae and M. fortuitum were presented in seventeen and twelve NTM isolates from the collected samples. There is evidence that NTM infections in endemic settings may contribute to the dissemination of various diseases and the control of tuberculosis. In spite of this, further research is needed to evaluate the clinical significance of NTM isolates.

Background and Objectives: The role of microRNAs (miRNAs) in tuberculosis infection is well established. As microRNAs are able to change expression profiles according to different conditions, they can be useful biomarkers. Iranians and Afghans with tuberculosis were studied for three immune-related miRNAs (miR-let-7f, miR-125a, and miR-125b). Materials and Methods: A total of 60 Iranian and Afghan patients with active pulmonary TB were enrolled in the Pulmonary Department of the Pasteur Institute of Iran. Serum and sputum samples were collected simultaneously from all participants. A Real-time PCR was conducted to detect differentially expressed miRNAs. Results: Iranian (P

Abstract Background A mixed pulmonary infection of Mycobacterium bacteremicum and three different isolates of nontuberculous mycobacteria (NTM) is an unusual clinical manifestation and have not yet been indicated. In this case report, we reported four isolates of NTM using phenotypic and genotypic test of pulmonary sample in Tehran, Iran. Case presentation We report a case of severe pulmonary disease in a 19-year-old male patient with productive cough, shortness of breath, and low-grade fever for several weeks. The C-reactive protein (CRP) level (80.2 mg/L) and erythrocyte sedimentation rate (ESR) (95 mm/h) were high. The computed tomographic scan indicated bronchiectasis, nodular opacities, consolidation, and cavitary lesions on both sides. The result of purified protein derivative (PPD) test was equal to 15 mm. The sequences of hsp65, rpoB, and 16S rDNA genes indicated more than 99% homology to four isolates of nontuberculous mycobacteria (NTM), including Mycobacterium fortuitum, M. chelonae, M. mucogenicum, and M. bacteremicum. We found that all four strains were susceptible to amikacin, cefoxitin, ciprofloxacin, clarithromycin, imipenem, and linezolid. The patient was treated with ciprofloxacin, clarithromycin, and amikacin, along with Montelukast, for five months. Conclusion We report a case of severe pulmonary infection by four isolates of NTM. After treatment, the patient reported complete resolution of the signs and a weight gain of 5 kg; also, the CRP and ESR were normal. Nine months after the infection diagnosis, a new CT scan revealed further improvements.

Some organisms may modulate a healthy state or cause disorders by disruption or induction of several signaling pathways in human body. According to recent evaluations, numerous metabolic disorders such as diabetes, obesity, cardiovascular diseases, mental disorders, and cancers are as the result of bacterial interactions with the host. Various species of the bacteria, called commensal microbiota, live in normal human body which modulate some of the host critical functions by different mechanisms. Induction of epigenetic modifications in host cells that are important in the maintenance of homeostasis or induction of disorders is amongst these mechanisms. Indeed, different factors may induce epigenetic modifications. For example, diet and its effect on microbiota community may epigenetically change the expression of some specific genes. Such modifications may also be dangerous and inherited to next generations. The current review tried to explain the inter-talk between gut microbiota and epigenetic modifications in health and disorders.

Background: Obesity is a complex disorder influenced by various genetic and environmental factors. It has been shown that gut microbiota, which colonizes gastrointestinal tract, has a substantial role as an environmental factor in the pathophysiology of obesity. Since the composition of gut microbiota alters with regard to different criteria, such as ethnicity, geographical location, diet, lifestyle, age, and gender, we aimed to determine firmicutes/bacteroidetes (F/B) ratio and the abundance of important gut microbiota members, Akkermansia muciniphila, Faecalibacterium prausnitzii, Roseburia, Bifidobacterium, and Prevotella in Iranian obese and normal weight individuals, for the first time. Methods: In this study, 50 normal and 50 obese subjects were recruited and classified based on their BMI into normal weight and obese groups. Stool samples were collected. Following DNA extraction from the samples, quantitative PCR was conducted based on 16s rDNA universal primers. Finally, the correlation between the bacterial abundance and obesity was analyzed by statistical analyses. Results: We observed a significant increase of F/B ratio in the obese group, compared to the normal weight group (p = 0.002). Although A. muciniphila (p = 0.039) and Bifidobacterium (p = 0.049) abundance significantly decreased, the abundance of F. prausnitzii (p = 0.046) significantly elevated with BMI increase in the studied groups. Conclusion: Owing to the importance of the gut microbiota composition in obesity development, determination and targeted restoration of gut microbiota pattern could be valuable in the control and treatment of obesity in certain populations.

Extracellular vesicles (EVs) cause effective changes in various domains of life. These bioactive structures are essential to the bidirectional organ communication. Recently, increasing research attention has been paid to EVs derived from commensal and pathogenic bacteria in their potential role to affect human disease risk for cancers and a variety of metabolic, gastrointestinal, psychiatric, and mental disorders. The present review presents an overview of both the protective and harmful roles of commensal and pathogenic bacteria-derived EVs in host-bacterial and interbacterial interactions. Bacterial EVs could impact upon human health by regulating microbiota–host crosstalk intestinal homeostasis, even in distal organs. The importance of vesicles derived from bacteria has been also evaluated regarding epigenetic modifications and applications. Generally, the evaluation of bacterial EVs is important towards finding efficient strategies for the prevention and treatment of various human diseases and maintaining metabolic homeostasis.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the outbreak of a new viral respiratory infection. It has been demonstrated that the microbiota has a crucial role in establishing immune responses against respiratory infections, which are controlled by a bidirectional cross-talk, known as the “gut-lung axis.” The effects of microbiota on antiviral immune responses, including dendritic cell (DC) function and lymphocyte homing in the gut-lung axis, have been reported in the recent literature. Additionally, the gut microbiota composition affects (and is affected by) the expression of angiotensin-converting enzyme-2 (ACE2), which is the main receptor for SARS-CoV-2 and contributes to regulate inflammation. Several studies demonstrated an altered microbiota composition in patients infected with SARS-CoV-2, compared to healthy individuals. Furthermore, it has been shown that vaccine efficacy against viral respiratory infection is influenced by probiotics pretreatment. Therefore, the importance of the gut microbiota composition in the lung immune system and ACE2 expression could be valuable to provide optimal therapeutic approaches for SARS-CoV-2 and to preserve the symbiotic relationship of the microbiota with the host.

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria and their RNA content have recently received increasing attention as novel mediators of host-guest intercellular and interspecies communication. These kinds of vesicles allow not only the export of proteins, but also of DNA and other small RNAs. We previously reported that the production of bacterial vesicles could represent a way to communicate with the surrounding environment. This general mechanism, exploited by bacteria and viruses, allows conveying “messages” to the surrounding cells and tissues, thus leading to the manipulation of the host immune response. Many functions attributed to OMVs are a consequence of their high capability to survive in different environmental stressors and to enter into cells quite easily. As these properties can be exploited to advantage human health, in this review, we summarized the papers that reported the use of OMVs as modulators of cellular activities through the involvement of the RNAs contained within. We also discussed what has been done with OMVs and what remains to be discovered in order to prompt the investigations toward the complete elucidation of the role and functions of these vesicles.

Background and Objectives: Drug resistance in Pseudomonas aeruginosa strains has become a worldwide problem, and efflux pumps are one of the major resistance mechanisms in this bacterium. The aim of this study was to identify the mutation in mexA and mexB pumps and to investigate the expression level of mexA pump in the isolates from burn patients. Methods: This study was conducted as a descriptive study on 100 isolates of P. aeruginosa isolated from patients hospitalized in Shahid Motahari Hospital during 2014-2015. Antibiogram tests were performed using disc diffusion (according to CLSI guidelines). The inhibitory effect of carbonyl cyanide 3-chlorophenylhydrazone (CCCP), was assessed by broth microdilution method. Mutation in mexA and mexB genes, was detected by PCR and sequencing, and the expression level of mexA gene, was evaluated by real-time PCR and 2−ΔΔCT formula. Results: Ninety-five out of 100 isolates of P. aeruginosa, were resistant to imipenem. Sixteen isolates had response to the inhibitory effect, and a 4-fold reduction was observed in MIC results at the presence of this inhibitor. In one isolate, glycine was replaced by aspartic acid at position 257 of mexB protein sequence, but no change was seen in MexA. All isolates had mexA and mexB genes. Twenty percent of the isolates showed overexpression in mexA gene. Conclusion: According to the results of this study, the antibiotic resistance as a result of overexpression of efflux pump, is of great concern. Hence, infection control by accurate management of drug prescription and identification of resistant isolates, is essential to prevent the spread of resistance.

The increasing prevalence of drug-resistant Pseudomonas aeruginosa in burned patients is one of the main public health problems worldwide. Although drug-resistant P. aeruginosa in burn units is frequent in some countries and unusual in others, the level of this conditions is not precisely known in Iran. Imipenem is one of the most potent agents against P. aeruginosa. Imipenem resistance is a major obstacle to treatment of P. aeruginosa infections. We aimed to determine the true prevalence of imipenem-resistant P. aeruginosa in Iranian burned patients according to the Preferred Reporting Items for Meta-Analyses statement. Moreover, resistance to several potent anti-P. aerugi nosa drugs were indicated according to the Clinical and Laboratory Standards Institute guidelines for the disc diffusion method. Several databases including Web of Science, Scopus, PubMed, Scientific Information Database, Magiran, Iranmedex, and science direct were searched to get studies addressing drug-resistant P. aeruginosa in Iranian burned patients from March 2006 to May 2015. A total of 34 reports available from different areas of Iran were included in the current study. The meta-analyses showed that 54.9% of P. aeruginosa were resistant to imipenem. The most common resistance was seen against ceftazidime (66.9%), followed by ciprofloxacin (52.9%) and cefepime (52.3%). It is necessary to know the epidemiology of drug-resistant P. aeruginosa because it can promote control strategies for decreasing their prevalence. The high incidence of drug-resistant P. aeruginosa in Iran emphasizes the need for precise drug susceptibility testing, continuous monitoring of drug resistance, especially in burn units, use of sensitive methods for the laboratory diagnosis, and close relation between physician and laboratories.

Stenotrophomonas maltophilia is an environmental Gram-negative bacterium that has rapidly emerged as an important nosocomial pathogen in hospitalized patients. Treatment of S. maltophilia infections is difficult due to increasing resistance to multiple antibacterial agents. The purpose of this study was to determine the phenotypic and genotypic characterization of S. maltophilia isolates recovered from patients referred to several hospitals. A total of 164 clinical isolates of S. maltophilia were collected from hospitals in various regions in Iran between 2016 and 2017. Antibiotic susceptibility testing was performed by disc diffusion method and E-test assay according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The ability of biofilm formation was assessed with crystal violet staining and then, biofilm-associated genes were investigated by PCR-sequencing method. The presence of L1 (a metallo-β-lactamase), L2 (a clavulanic acid-sensitive cephalosporinase), sul1 and sul2 (resistance to Trimethoprim/Sulfamethoxazole), Smqnr (intrinsic resistance to quinolones), and dfrA genes (dihydrofolate reductase enzyme that contributes to trimethoprim resistance) was also examined by PCR-sequencing. Relative gene expression of smeDEF efflux pump was assessed by real-time PCR. Genotyping was performed using the multi-locus sequencing typing (MLST) and repetitive extragenic palindromic-PCR (Rep-PCR). Isolates were resistant to imipenem (100%), meropenem (96%), doripenem (96%), and ceftazidime (36.58%). Notably, 5 (3.04%) isolates showed resistant to trimethoprim-sulfamethoxazole (TMP-SMX), an alarming trend of decreased susceptibility to TMP-SMX in Iran. Minocycline and levofloxacin exhibited the highest susceptibility of 91.46 and 99.39%, respectively. Using the crystal violet staining, 157 (95.73%) isolates had biofilm phenotype: 49 (29.87%), 63 (38.41%), and 45 (27.43%) isolates were categorized as strong-, moderate- and weak-biofilm producer while 7 isolates (4.26%) were identified a non-biofilm producer. Biofilm genes had an overall prevalence of 145 (88.41%), 137 (83.53%), and 164 (100%) of rmlA, rpfF, and spgM, respectively. L1, L2, Smqnr, sul1, and sul2 resistance genes were detected in 145 (88.41%), 156 (96.12%), 103 (62.80%), 89 (54.26%), and 92 (56.09%) isolates, respectively. None of the S. maltophilia isolates were positive for dfrA12, dfrA17, and dfrA27 genes. Gene expression analysis showed that smeD efflux system was overexpressed in two out of the five clinical isolates (40%) that showed resistance to TMP-SMX. Most of the isolates were genetically unrelated. Two new sequence types (ST139 and ST259) were determined. Our results showed that TMP-SMX was still an effective antibiotic against S. maltophilia. The findings of the current study revealed an increasing prevalence of antibiotic resistance and biofilm genes in clinical S. maltophilia isolates in Iran.

Background and Objectives: Escherichia coli (E.coli) is an opportunistic Gram-negative bacterium, which causes common nosocomial infections, including pneumonia, septicemia, meningitis, diarrhea, bacteremia, etc. Antibiotic resistance is a serious problem for human health, so that the World Health Organization in called the year 2011 as the year of antibiotic resistance. One of the reasons of these resistances is production of broad-spectrum β-lactamases (ESBLs), which are able to hydrolyze broad-spectrum β-lactam antibiotics. This study was performed aiming at determining the prevalence of cefotaxime-resistant strains and evaluating the ESBL genes (bla TEM, bla SHV and blaCTX-M) in E. coli isolates. Methods: In this cross-sectional study during a 5-month period (April to September 2014), specimens sent to the laboratory of Ali-Ibne Abi Talib Hospital of Qom, such as blood, urine, wound, etc., were examined. After identification and isolation of E.coli strains, their antibiotic resistance and ESBL production were determined by disk diffusion method, MIC, and combination disk method according to CLSI guidline. Then, detection of blaCTX-M, SHV, and TEM genes was performed using PCR. Results: Of 160 isolated E. coli and based on the results of disk diffusion and MIC, 31 (19%) isolates were resistant to cefotaxime. Also, based on the phenotypic results, 24 (77%) cefotaxime-resistant ESBL-producing strains, were idetified. The blaCTX-M, blaTEM, and blaSHV genes were determined in 90%, 42%, and 3% of the strains, respectively. Conclusion: The results revealed that prevalence of ESBL-producing E .coli is high. Therefore, there is a need to manage the use of antibiotics and identify the source and distribution of β-lactamase-producing isolates.

Background: The infections caused by drug resistant strains of Klebsiella pneumoniae are becoming an important health problem worldwide. There are several reports on antimicrobial resistant status of K. pneumoniae in Iran. However, a comprehensive analysis on drug-resistant K. pneumoniae from different parts of Iran has not yet been performed. Methods: The searches were done according to several English and Persian databases including PubMed, Scopus, Iranmedex, and SID to identify studies addressing antibiotic resistant K. pneumoniae in Iran from Jan 1998 to Nov 2014. Comprehensive Meta-Analysis (V2.2, Biostat) software was used to analyze the data. Results: The incidence rate of imipenem and ceftazidime resistance in K. pneumoniae isolates was 3.2% (95% confidence interval [CI], 1.5-6.5) and 55.7% (95% CI, 46.9-64.1), respectively. The highest rate of resistance in isolates of K. pneumoniae was seen against ampicillin (82.2%), aztreonam (55.4%) and nitrofurantoin (54.5%). Conclusion: There is a relatively high prevalence of drug resistant K. pneumoniae isolates in Iran. Thus, a high degree of awareness among physicians and microbiologists, active infection control committee, appropriate antimicrobial therapy, improvement of hygiene condition and monitoring of drug resistant isolates are urgently needed in order to better control the emergence and spread of drug-resistant K. pneumoniae isolates in hospital settings.

Background: The increasing pattern of Multi-Drug Resistant (MDR) bacteria has limited therapeutic options especially for nosocomial isolates of Klebsiella pneumoniae. Therefore, the aim of this study was the molecular detection of 16S rRNA methylase and blaCTX-M-15 among K. pneumoniae strains isolated from hospitalized patients in Mofid, Imam Hossein and Taleghani hospitals. Materials and Methods:This study was done with 110 K.pneumoniae isolated of hospitals in Tehran, Iran. Antibiotic susceptibility tests were carried out by Kirby-Bauer disc diffusion and broth microdilution methods according to CLSI guidelines. ESBL, AmpC and KPC enzymes were detected by CDDT and MHT methods and the armA, rmtB, rmtC, rmtD and blaCTX-M-15 genes were detected by PCR and sequencing techniques. Typing of antibiotic resistance isolates was carried out by PFGE technique. Results: In this study, Fosfomycin, colistin and tigecycline were more active than other antibiotics. Among the 110 K. pneumoniae strains, 60(54.5%), 33(30%) and 5(4.5%) were ESBL, Amp-C and KPC positive, respectively. The existence of blaCTX-M-15, armA and rmtC was detected in 40(36.3%), 15 (13.6%) and 2 (1.8%) respectively. Of 15 representative armA-producing K. pneumoniae isolates analyzed by PFGE, 9 different pulsotypes (PF1–9) were identified with Dice coefficients of &ge90% similarity. Conclusions: High-level aminoglycoside resistance in human pathogens result of 16S rRNA methylases is one of the serious concerns in Iran.