Global mapping of antibiotic resistance rates among clinical isolates of Stenotrophomonas maltophilia: a systematic review and meta-analysis.

INTRODUCTION: Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge. AIM: The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies. METHOD: A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis. RESULT: Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010. CONCLUSIONS: Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.

Novel strategies for inhibition of bacterial biofilm in chronic rhinosinusitis.

An important role has been recently reported for bacterial biofilm in the pathophysiology of chronic diseases, such as chronic rhinosinusitis (CRS). CRS, affecting sinonasal mucosa, is a persistent inflammatory condition with a high prevalence around the world. Although the exact pathological mechanism of this disease has not been elicited yet, biofilm formation is known to lead to a more significant symptom burden and major objective clinical indicators. The high prevalence of multidrug-resistant bacteria has severely restricted the application of antibiotics in recent years. Furthermore, systemic antibiotic therapy, on top of its insufficient concentration to eradicate bacteria in the sinonasal biofilm, often causes toxicity, antibiotic resistance, and an effect on the natural microbiota, in patients. Thus, coming up with alternative therapeutic options instead of systemic antibiotic therapy is emphasized in the treatment of bacterial biofilm in CRS patients. The use of topical antibiotic therapy and antibiotic eluting sinus stents that induce higher antibiotic concentration, and decrease side effects could be helpful. Besides, recent research recognized that various natural products, nitric oxide, and bacteriophage therapy, in addition to the hindered biofilm formation, could degrade the established bacterial biofilm. However, despite these improvements, new antibacterial agents and CRS biofilm interactions are complicated and need extensive research. Finally, most studies were performed in vitro, and more preclinical animal models and human studies are required to confirm the collected data. The present review is specifically discussing potential therapeutic strategies for the treatment of bacterial biofilm in CRS patients.

Mutation in mgrB is the major colistin resistance mechanism in Klebsiella pneumoniae clinical isolates in Tehran, Iran.

Colistin is considered as one of a last resort antimicrobial agent against multidrug-resistant Gram-negative bacteria including Escherichia coli and Klebsiella pneumoniae. However, the recent emergence of colistin resistance (ColR) worldwide that severely restricts therapeutic options is a serious threat to global public health. In this study we have investigated the molecular determinants in ColR K. pneumoniae isolates collected from clinical specimens. A total of 98 E. coli and 195 K. pneumoniae clinical isolates were collected from two hospitals from August 2018 to December 2019 in Tehran, Iran. Colistin susceptibility and minimum inhibitory concentrations (MIC) were determined according to the Clinical and Laboratory Standards Institute by disk diffusion method, and microdilution method, respectively. For isolates with colistin MIC ≥4 µg mL-1, PCR was performed for the detection of mcr-1 to mcr-4 genes. Moreover, nucleotide sequences of mgrB, phoP, phoQ, pmrA, and pmrB genes were determined by sequencing. Finally, the transcriptional level of pmrK and pmrC genes was evaluated by quantitative reverse transcription PCR (RT-qPCR). None of the E. coli isolates were resistant to colistin while 21 out 195 K. pneumoniae isolates were identified as resistant, 19 of which carried mutation in the mgrB gene. Three different mutations were observed in the pmrB gene in 3 K. pneumoniae isolates. None of the ColR isolates showed alternations in pmrA, phoP, and phoQ genes. Furthermore, none of the plasmid-encoding genes were detected. Transcriptional level of the pmrK gene increased in all ColR isolates meanwhile, pmrC overexpression was detected in 16 out 21 (76.19%) isolates. Eventually, all ColR isolates were susceptible to tigecycline. Our results demonstrated that the alternation of mgrB gene is the main mechanism related to colistin resistance among ColR K. pneumoniae isolates in this study.

The controversial association of gut and urinary microbiota with kidney stone formation.

Nephrolithiasis (kidney stones) is one of the most common chronic kidney diseases that are typically more common among adult men comparing to adult women. The prevalence of this disease is increasing which is influenced by genetic and environmental factors. Kidney stones are mainly composed of calcium oxalate and urinary oxalate which is considered a dangerous factor in their formation. Besides diverse leading reasons in the progression of nephrolithiasis, the gut and urinary microbiome has been recognized as a major player in the development or prevention of it. These microbes produce metabolites that have diverse effects on host biological functions. Therefore, Changes in the composition and structure of the microbiome (dysbiosis) have been implicated in various diseases. The present review focuses on the roles of gut and urinary in kidney stone formation.

An overview of possible pathogenesis mechanisms of Alternaria alternata in chronic rhinosinusitis and nasal polyposis.

Chronic Rhinosinusitis (CRS) is a multifactorial disease, and different etiologies like metabolism and immunity disorders, bacterial superantigens, biofilms, and fungal allergens are known to develop this disease, especially the CRS with nasal polyps. Alternaria alternata (Alternaria) is one of the most prevalent airborne fungal species in the nasal discharge, which might have vigorous immunologic activities in nasal epithelial cells and play an essential role in the pathogenesis of CRS. Moreover, the interaction between this fungus and the innate and adaptive immune systems leads to the development of chronic inflammation. This inflammation may consequently instigate the CRS and nasal polyposis. The attenuation of surfactant protein synthesis or intracellular reserves and mucus hypersecretion could prevent the clearance of Alternaria from sinuses and may be correlated with colonization and re-infection of airborne fungi. Furthermore, higher expression of cathelicidin, thymic stromal lymphopoietin, toll-like receptors, and T helper 2-dominant immune responses can result in an IgE-mediated pathway activation and eosinophils degranulation. Moreover, higher local Alternaria-specific IgE was shown to be correlated with eosinophilic cationic proteins and might relate to nasal polyps. However, the role of genetic and environmental factors affecting CRS and nasal polyposis is not well studied. Likewise, further animal and clinical studies are required to better understand the role of Alternaria in CRS disease. The current article reviews the recent findings around the Alternaria-induced CRS and nasal polyposis.

The Effects of Antioxidant Vitamins on Proinflammatory Cytokines and Some Biochemical Parameters of Power Plant Workers: A Double-Blind Randomized Controlled Clinical Trial.

Some epidemiological studies have suggested that exposure to extremely low-frequency magnetic fields (ELF-MFs) can affect the immune system. This study aimed to investigate the effects of antioxidant vitamin consumption on proinflammatory cytokines and biochemical parameters changes. In this randomized, controlled double-blinded trial study, power plant workers exposed to ELF-MFs were enrolled based on inclusion criteria. Ninety-one eligible subjects were randomly divided into four groups: the first group (400 units of vitamin E/day), second group (1,000 mg of vitamin C/day), third group (400 units of vitamin E and 1,000 mg of vitamin C/day), and control group. The intervention was conducted for 3 months. Proinflammatory cytokines interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α), and biochemical parameters (fasting blood sugar, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-c], total protein, and albumin) were measured among the participants' serums, before and after the intervention. The mean level of IL-6 in all vitamin-receiving groups, the mean level of IL-1ß in vitamin C and E&C groups, and the mean level of TNF-α in the vitamin C group, decreased significantly after intervention. The arithmetic means of the effect sizes for IL-1ß, IL-6, and TNF-α were 0.71, 0.57, and 0.2, respectively. The level of HDL-c in the vitamin E and vitamin E&C groups and the level of triglyceride in the vitamin C group significantly increased after the intervention. Taking antioxidant vitamins can prevent an increase of proinflammatory cytokines induced by prolonged exposure to ELF-MFs. Bioelectromagnetics. 2021;42:18-26. © 2020 Bioelectromagnetics Society.

Prevalence and molecular mechanisms of colistin resistance in Acinetobacter baumannii clinical isolates in Tehran, Iran.

Colistin is one of the last remaining active antibiotics against multidrug resistant Gram-negative bacteria. However, several recent studies reported colistin-resistant (ColR) Acinetobacter baumannii from different countries. In the current study, we investigated molecular mechanisms involved in colistin resistance in A. baumannii isolates from different clinical samples.A total of 110 clinical A. baumannii isolates were collected from two hospitals in Tehran. Minimum inhibitory concentrations (MICs) were determined by broth microdilution according to the Clinical and Laboratory Standards Institute. For the ColR isolates, mutation was detected in pmrA, pmrB, lpxA, lpxC, and lpxD genes using the polymerase chain reaction (PCR) and sequencing. Moreover, the relative expression of the pmrC gene was calculated using quantitative reverse transcription PCR. Three colistin resistant isolates were identified with MIC between 8 and 16 µg/mL and were resistant to all the tested antimicrobial agents. All the three isolates had a mutation in the pmrB, pmrA, lpxA, lpxD, and lpxC genes. Moreover, the overexpression of pmrC gene was observed in all isolates. Our results showed that the upregulation of the PmrAB two component system was the primary mechanism linked to colistin resistance among the studied colistin resistant A. baumannii isolates.

Prevalence and molecular epidemiology of ceftaroline non-susceptible methicillin-resistant Staphylococcus aureus isolates, first clinical report from Iran.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major pathogens in Iran with a high prevalence and a high level of antibiotic resistance. Ceftaroline is a fifth generation cephalosporin binding and inhibiting penicillin binding protein (PBP2a). METHODS: In the present study, 228 clinical MRSA isolates were collected from four cities of Iran and their susceptibility to ceftaroline was evaluated by E-test and the disk diffusion method. RESULTS: Our results showed a high susceptibility rate (97.3%) to ceftaroline in MRSA strains from Iran. Six isolates were found to be ceftaroline non-susceptible (CPT-NS) with Minimum inhibitory concentration (MIC) ≥2 µg/mL. All CPT-NS isolates were isolated from blood and tracheal aspirate and belonged to SCCmec type III as well as agr type I and were all susceptible to vancomycin. Out of six isolates, three, two and one belonged to spa type t030, t4864, and t969, respectively. Vancomycin, quinupristin/dalfopristin, linezolid, chloramphenicol, and tigecycline were the most active agents against CPT-NS isolates. CONCLUSION: Due to the broad-spectrum activity and low toxicity of ceftaroline as well as the increased rate of vancomycin resistance among MRSA strains in recent years, ceftaroline can be considered as a novel approach to treat MRSA-induced infections.

Mycobacterium avium complex infection in patients with human immunodeficiency virus: A systematic review and meta-analysis.

BACKGROUND: Mycobacterium avium-intracellulare complex (MAC) is one of the leading causes of death among people living with human immunodeficiency virus (HIV). The current study was aimed to determine the frequency of MAC infection in patients infected with HIV. METHODS: Embase, PubMed, and Web of Science were searched for relevant studies. All statistical analyses were performed by STATA version 14. RESULTS: From 6,627 retrieved articles, 23 were included in the final analysis. A total of 18,463 patients with HIV were included in the analysis. The frequency of MAC infection in patients with HIV was found to be 10.6% (95% confidence interval, 6.9-14.2). CONCLUSION: The relatively large fractions of HIV-infected patients were coinfected with MAC, which may poses significant public health problems. Continued progress in the development of rapid diagnostic methods and preventive therapy for MAC should lead to further improvements in survival and quality of life in patients with HIV.

Molecular characterization of nontuberculous mycobacteria in hospital waters: a two-year surveillance study in Tehran, Iran.

Microbiological control of hospital waters as one of the main sources of nontuberculous mycobacteria (NTM) is important for the prevention of NTM-associated illness. This study aimed to investigate the prevalence of NTM in the hospital water systems of Tehran, Iran. A total of 218 samples from different hospital waters (i.e., tap water and medical devices such as humidifying cup of oxygen manometer, dialysis devices, nebulizers, and dental units) were included in this study. Phenotypic and molecular tests were used to identify the isolated organisms to species level. Of 218, 85 (39.0%) samples at 37 °C and 87 (40.0%) samples at 25 °C were identified as NTM. Using hsp65-sequencing method, Mycobacterium lentiflavum was the most frequently encountered, followed by M. gordonae and M. paragordonae. No significant difference was seen in frequency and species in mycobacteria isolated at 37 °C and 25 °C temperatures. Humidifying cup of oxygen manometer had the most contaminated water among the investigated water distribution systems in hospitals. Isolation of NTM from hospital water sources is a serious public health problem in Iran and merits further attention by health authorities. Establishment of microbiological monitoring systems for hospital waters and expanding the number of facilitated laboratories are strongly recommended.

Determination of antibiotic resistance pattern and virulence genes in Escherichia coli isolated from bovine with subclinical mastitis in southwest of Iran.

The aims of the present study were to investigate the prevalence of some virulence genes and also determine the antimicrobial resistance pattern of E. coli isolated from bovine with subclinical mastitis. The milk of 502 cows was collected from 8 dairy herds in the southwest of Iran. Conventional biochemical tests were used for identification of E. coli at the species level. Antimicrobial susceptibility patterns of E. coli isolates were determined by disc agar diffusion method and polymerase chain reaction (PCR) was used for detection of seven virulence genes including f17A, afaE-8, afaD-8, eaeA, cnf1, cnf2, and iucD. Seventy (13.94%) isolates of E. coli were identified in 502 milk samples. The highest rate of resistance was observed against tetracycline (18.6%), while none of the isolates were resistant to streptomycin. Eight (11.5%) out of 70 E. coli isolates carried at least one of the virulence genes. The afaD-8 was the most prevalent gene detected in 5 (7.1%) isolates. The afaE-8, iucD, and eaeA were detected in 3, 3, and 2 isolates respectively. Low prevalence of virulence factors may be indicating that most of the E. coli isolates originated from the commensal flora of cows and enter to the udders via environment contamination with feces.

Molecular characterization of Staphylococcus aureus isolates from southwest of Iran using spa and SCCmec typing methods.

Staphylococcus aureus remains a major cause of nosocomial infection worldwide. Characterization of S. aureus isolates circulating in the southwest of Iran will contribute to understand and control the spread of the strains in this area. spa and SCCmec typing methods were used for genotyping of 125 S. aureus isolates obtained from two teaching hospitals in Ahvaz. Drug susceptibility testing was performed by using disk diffusion method. Frequency of the methicillin resistant S. aureus (MRSA) isolates was 39% (n = 34) and 27% (n = 10) in Emam Khomeini and Golestan hospitals, respectively. Except for Erythromycin, MRSA strains showed high rate of resistance to antimicrobial agents including penicillin (100%), norfloxacine (80%), azitromycin (80%), ciprofloxacin (80%), gentamycin (77%), cotrimoxazole (75%), cephotaxime. All isolates were sensitive to vancomycin. Out of 44 MRSA strains, 39 (88.5%) were SCCmec III, three (7%) were IVc and two (4.5%) of them were nontypeable. spa types t037 (26 isolates; 59%), and t1149 (25 isolates; 31%) were the most dominant types found in MRSA and methicillin sensitive S. aureus (MSSA) strains, respectively. We found SCCmec type III as the most prominent type indicating that most of the studied bacterial population had hospital origin. spa type t037, the most frequent genotype in this study were significantly (100%) associated with MRSA. For the first time we are reporting spa types t692, t706 and t018 from Iran and t342, t704, t2622, t5598, t11270 and t2864 from Asia. Moreover we are reporting types t6871 and t2684 for the second time in the world.

Detection of biofilm related genes, classical enterotoxin genes and agr typing among Staphylococcus aureus isolated from bovine with subclinical mastitis in southwest of Iran.

Staphylococcus aureus by producing biofilm and facilitating chronic infection is a common cause of mastitis in cows and thereby can cause food poisoning by production of enterotoxins in milk. The agr typing method is an important tool for epidemiological investigation about S. aureus. The aims of the present study were to detect biofilm related genes, 5 classical enterotoxin genes and the agr types among S. aureus isolates. The ability of S. aureus isolates to produce biofilm was evaluated by modified CRA plate. Six biofilm related adhesion genes (icaD, icaA, fnbA, bap, clfA and cna), five classical enterotoxin genes (sea, seb, sec, sed and see) and tst-1 gene were detected by PCR methods. Multiplex-PCR was used to determination of the agr groups. 55 out of 80(68.8%) S. aureus isolates were biofilm producer. The icaD gene was detected in 70 (87.5%) of isolates. The prevalence rates of fnbA, icaA, clfA, cna and bap were 72.5, 56.25, 50, 22.5, and 5% respectively. The agr group I and III were detected in 57.5% 25% of studied isolates. The sea, sed and tst-1 genes were found in 10%, 7.5% and 1.25% of isolates respectively. The majority of S. aureus were able to produce biofilm. Significant associations were observed between presence of the icaD, icaA, fnbA, clfA and the cna genes as well as biofilm formation. The present study revealed that isolates with the agr type III are more potent for biofilm production. Our data supported a possible link between the agr types and certain SE genes.

Investigating the antimicrobial and anti-inflammatory effects of Lactobacillus and Bifidobacterium spp. on cariogenic and periodontitis pathogens.

Background: The use of probiotics is emerging as an innovative approach to managing oral health issues and mediating the immune system. The current study assessed the in vitro impacts of non-orally isolated probiotics on periodontitis and tooth decay pathogens. Methods: Briefly, the persistence of probiotics in exposure to oral cavity enzymes, hydrogen peroxide, and saliva samples was examined. It was also investigated the biofilm formation and aggregation ability of probiotics, the adherence of probiotics in human gingival fibroblast cell (HGFC) lines and molar teeth samples, and the potential of probiotics to co-aggregate with oral pathogens. Additionally, the current study evaluated the effects of live probiotics on virulence gene expression, biofilm production of main oral pathogens, and changes in inflammation markers. Results: The probiotics remained alive when exposed to enzymes in the oral cavity, hydrogen peroxide, and saliva at baseline, 1, 3, and 5 h after incubation at 37°C (p-value <0.05). Probiotics demonstrated to produce biofilm and aggregation, as well as adherence to HGFCs and maxillary molars (p-value >0.05). They showed significant co-aggregation with oral pathogens, which were recorded as 65.57% for B. bifidum 1001 with S. mutans, 50.06% for B. bifidum 1005 with P. gingivalis, 35.6% for L. plantarum 156 with F. nucleatum, and 18.7% for B. longum 1044 with A. actinomycetemcomitans after 8 h of incubation. A balance between pro-inflammatory and anti-inflammatory cytokines, along with inhibition of biofilm formation and changes in virulence gene transcripts, were observed. However, most of these changes were not statistically significant (p-value >0.05). Conclusion: This study demonstrated the direct link between adhesiveness, aggregation, and biofilm formation with probiotic antibacterial activity. In addition to the careful selection of suitable probiotic strains, the concentration and origin of probiotic isolates should be considered.

Prevalence of colistin resistance in clinical isolates of Acinetobacter baumannii: a systematic review and meta-analysis.

INTRODUCTION: The development of colistin resistance in Acinetobacter baumannii during treatment has been identified in certain patients, often leading to prolonged or recurrent infections. As colistin, is the last line of therapy for A. baumannii infections that are resistant to almost all other antibiotics, colistin-resistant A. baumannii strains currently represent a significant public health threat, particularly in healthcare settings where there is significant selective pressure. AIM: The aim of this study was to comprehensively determine the prevalence of colistin resistance in A. baumannii from clinical samples. Regional differences in these rates were also investigated using subgroup analyses. METHOD: The comprehensive search was conducted using "Acinetobacter baumannii", "Colistin resistant" and all relevant keywords. A systematic literature search was performed after searching in PubMed, Embase, Web of Science, and Scopus databases up to April 25, 2023. Statistical analysis was performed using Stata software version 17 and sources of heterogeneity were evaluated using I2. The potential for publication bias was explored using Egger's tests. A total of 30,307 articles were retrieved. After a thorough evaluation, 734 studies were finally eligible for inclusion in the present systematic review and meta-analysis. RESULT: According to the results, the prevalence of resistance to colistin among A. baumannii isolates was 4% (95% CI 3-5%), which has increased significantly from 2% before 2011 to 5% after 2012. South America had the highest resistance rate to this antibiotic. The broth microdilution method had the highest level of resistance, while the agar dilution showed the lowest level. CONCLUSIONS: This meta-analysis found a low prevalence of colistin resistance among A. baumannii isolates responsible for infections worldwide from 2000 to 2023. However, there is a high prevalence of colistin-resistant isolates in certain countries. This implies an urgent public health threat, as colistin is one of the last antibiotics available for the treatment of infections caused by XDR strains of A. baumannii.

MIRU-VNTR analysis of the Mycobacterium tuberculosis isolates from three provinces of Iran.

BACKGROUND: Iran borders 2 high-burden tuberculosis (TB) countries to the east, and has the highest rates of TB in one of its eastern provinces. Limited information is available on the genetic diversity and transmission dynamics of Mycobacterium tuberculosis (MTB) in Iran. To examine the genetic diversity and transmission dynamics of MTB strains we genotyped a collection of isolates from different parts of Iran. METHODS: Standard 15-locus variable number tandem repeat (VNTR) typing was applied to genotype 121 MTB clinical isolates collected from 3 provinces of Iran, including Tehran (the capital of Iran), Sistan-Baluchestan (southeast province of Iran, with the highest rate of TB), and Kermanshah (western part of Iran with high TB/human immunodeficiency virus cases). Antibiotic susceptibility for all isolates was determined using the proportion method. RESULTS: Sixty-six distinct mycobacterial interspersed repetitive unit (MIRU)-VNTR patterns were detected among 121 isolates. Seventy-five strains grouped into 20 clusters, and 46 isolates were unique. The genetic diversity of strains from Sistan-Baluchestan was higher than that in the other provinces. All isolates from Tehran or Kermanshah that grouped into clusters shared identical patterns with Sistan-Baluchestan. The Hunter-Gaston discriminatory index (HGDI) was 0.972, indicating a high power of discrimination for MIRU-VNTR typing. The MIRU 16 and ETRA loci were designated as highly discriminative. The rates of monoresistance and multidrug resistance were 9.9% and 2.4%, respectively. CONCLUSIONS: MIRU-VNTR typing revealed high genetic diversity and suggests the possibility of transmission from Sistan-Baluchestan to other provinces of Iran. This method has potential for genetic analysis and for studying the transmission routes of TB.

Comparison of smear microscopy, culture, and real-time PCR for quantitative detection of Mycobacterium tuberculosis in clinical respiratory specimens.

BACKGROUND: As a rapid diagnostic technique, the real-time polymerase chain reaction (PCR) can detect Mycobacterium tuberculosis with a high sensitivity and specificity. However, further studies are needed to confirm it as a standard method. In this study, we evaluated the cyp141 gene for the detection and quantification of M. tuberculosis in respiratory specimens and compared the results with direct microscopy and culture. METHODS: Sputum samples (n = 247) were collected from patients of the different provinces of Iran. DNA was extracted from clinical specimens and H37Rv strain. After measuring the standard strain DNA concentration by NanoDrop and using the Avogadro number, the DNA was diluted 6 times in order to obtain 1 × 10(6) to 10 template copies. A Taqman probe was designed for detection of the target in a real-time PCR using the specific primers. RESULTS: Of 247 samples, 135 (55%) were culture-negative. Of 112 (45%) culture-positive samples, 88 were positive by both smear and culture and 24 were smear-negative but culture-positive. The real-time PCR enumerated 1.5E + 02 to 4.3E+ 03, 8.5E + 03 to 5.5E + 04, 7.2E + 04 to 1.1E + 06, and 1.2E + 06 to 8.1E + 07 M. tuberculosis cells in the specimens with smear-negative, 1-plus, 2-plus, and 3-plus codes, respectively. The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the real-time PCR were 90.2% (101/112), 97.8% (132/135), 97.1%, and 92.3%, respectively. CONCLUSIONS: The overall sensitivity and specificity, the results in comparison with those of the Xpert MTB/RIF kit, and the good correlation with molecular and phenotypic methods, show that cyp141 could be a good target for the quantification of M. tuberculosis in sputum and possibly other clinical specimens.

COVID-19: An Overview of SARS-CoV-2 Variants-The Current Vaccines and Drug Development.

The world is presently in crisis facing an outbreak of a health-threatening microorganism known as COVID-19, responsible for causing uncommon viral pneumonia in humans. The virus was first reported in Wuhan, China, in early December 2019, and it quickly became a global concern due to the pandemic. Challenges in this regard have been compounded by the emergence of several variants such as B.1.1.7, B.1.351, P1, and B.1.617, which show an increase in transmission power and resistance to therapies and vaccines. Ongoing researches are focused on developing and manufacturing standard treatment strategies and effective vaccines to control the pandemic. Despite developing several vaccines such as Pfizer/BioNTech and Moderna approved by the U.S. Food and Drug Administration (FDA) and other vaccines in phase 4 clinical trials, preventive measures are mandatory to control the COVID-19 pandemic. In this review, based on the latest findings, we will discuss different types of drugs as therapeutic options and confirmed or developing vaccine candidates against SARS-CoV-2. We also discuss in detail the challenges posed by the variants and their effect on therapeutic and preventive interventions.

Exploring the interplay between Fusobacterium nucleatum with the expression of microRNA, and inflammatory mediators in colorectal cancer.

Background: Fusobacterium nucleatum has been recognized as an important key bacterium in the cause and spread of colorectal carcinogenesis. Nevertheless, the clinical relevance of F. nucleatum in colorectal cancer (CRC) and its effect on immune factors and the tumor microenvironment have not been fully elucidated. Materials and methods: The frequency of F. nucleatum was measured in 100 paired tumor and normal tissue specimens by TaqMan quantification Real-Time Polymerase Chain Reaction (qPCR). The mRNA expression levels of cytokines (IL-6, IL-10, IL-12ß, IL-17, TNF-α, TLR-2, and TLR-4), and miRNAs (miR-21, miR-31) were examined. Eventually, any potential correlations between the molecular and clinicopathological features of the neoplastic samples and the abundance of F. nucleatum were analyzed. Results: The relative frequency of F. nucleatum was significantly increased in cancerous tissue compared to adjacent non-tumor tissues. Furthermore, the high level of F. nucleatum was significantly associated with histological grade III and IV CRC tissues (P = 0.027 and P = 0.022, respectively) and perineural invasion-positive patients (P = 0.037). In addition, the expression levels of IL-6, IL-17, TNF-α,IL-12ß, TLR-2, and TLR-4 as well as miR-21 and miR-31 showed a significant increase in the cancer group. A notable correlation was also observed between the high status of F. nucleatum and the expression of IL-6, TNF-α and miR-21. Conclusion: Our results emphasize the importance of F. nucleatum and changes in the expression of genes involved in CRC. Studying the microbial profile and gene expression changes in CRC patients may be a promising approach to improve screening methods and provide therapeutic strategies.

Evaluation of enterotoxigenic Bacteroides fragilis correlation with the expression of cellular signaling pathway genes in Iranian patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/ß-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC. MATERIALS AND METHODS: B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed. RESULTS: The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample. CONCLUSION: B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.