Prevalence, population structure, distribution of serotypes, pilus islands and resistance genes among erythromycin-resistant colonizing and invasive Streptococcus agalactiae isolates recovered from pregnant and non-pregnant women in Isfahan, Iran.

BACKGROUND: The information on antibiotic resistance and molecular features of Group B Streptococcus (GBS) are essential for epidemiological purposes as well as vaccine development. Therefore, we aimed to assess the antimicrobial resistance profiles and molecular characteristics of GBS isolates in Isfahan, Iran. A total number of 72 colonizing and invasive GBS were collected from pregnant and non-pregnant women. The GBS isolates were analyzed for resistance profiles, capsular genotyping, and detection of PI-1, PI-2a, PI-2b, hvgA, ermB, ermTR, lnuB and, mefA genes. Besides, erythromycin-resistant strains were subjected to multilocus sequence typing (MLST). RESULTS: The prevalence of colonizing and invasive GBS were 11 and 0.05%, respectively. The frequency of capsular serotypes was as follows: III (26.3%), Ia (20.83%), Ib and V (each 15.2%), IV (9.7%), II (8.3%), VII (2.7%), and VI (1.3%). Overall frequencies of PIs were as follows: PI-1, 37.5%, PI-1 + PI-2a, 30.5%, PI-1 + PI-2b, 29.1% and PI-2b, 2.7%. Two maternal colonizing GBS (2.6%) were hvgA positive and were belonged to ST-17/CPS-III/PI-1 + PI-2b lineage. Among 30(41.6%) erythromycin resistant GBS, 21 isolates (70%) harbored ermB gene, followed by ermTR (23.3%) and mefA (10%). One clindamycin-resistant isolate harbored the lnuB gene. MLST analysis revealed the following five clonal complexes (CCs) and nine STs: (CC-19/ST-335, ST-19, and ST-197), (CC-12/ST-43, ST-12), (CC-23/ST-163, ST-23), (CC-17/ST-17) and (CC-4/ST-16). CONCLUSION: The study shows an alarmingly high prevalence of erythromycin-resistant GBS in Iran. In addition, we report dissemination of ST-335/CPS-III clone associated with tetracycline and erythromycin resistance in our region. The distribution of capsular and pilus genotypes varies between invasive and colonizing GBS that could be helpful for vaccine development.

Immunometabolism in human brucellosis: An emerging field of investigation.

In recent years, extreme attention has been focused on the role of immunometabolism in the regulation of immune cell responses in healthy individuals during infection, autoimmunity, and cancer. In the infection biology area, it has been shown that there is a close relationship between the immune system and the host metabolic changes. Brucella species is an intracellular coccobacillus that infects humans and mammals, which led to brucellosis. Brucella species with host-specific evolutionary mechanisms allow it to hide from or manipulate cellular immunity and achieve intracellular persistence. Intracellular bacterial pathogens such as Brucella species also employ host cell resources to replicate and persist inside the host. Targeting these host systems is one promising strategy for developing novel antimicrobials to tackle intracellular infections. This study will summarize the role of metabolic reprogramming in immune cells and their relationship to brucellosis.

The emerging role of probiotics as a mitigation strategy against coronavirus disease 2019 (COVID-19).

COVID-19 is an acute respiratory infection accompanied by pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected millions of people globally. To date, there are no highly efficient therapies for this infection. Probiotic bacteria can interact with the gut microbiome to strengthen the immune system, enhance immune responses, and induce appropriate immune signaling pathways. Several probiotics have been confirmed to reduce the duration of bacterial or viral infections. Immune fitness may be one of the approaches by which protection against viral infections can be reinforced. In general, prevention is more efficient than therapy in fighting viral infections. Thus, probiotics have emerged as suitable candidates for controlling these infections. During the COVID-19 pandemic, any approach with the capacity to induce mucosal and systemic reactions could potentially be useful. Here, we summarize findings regarding the effectiveness of various probiotics for preventing virus-induced respiratory infectious diseases, especially those that could be employed for COVID-19 patients. However, the benefits of probiotics are strain-specific, and it is necessary to identify the bacterial strains that are scientifically established to be beneficial.

Role of microRNAs in Staphylococcus aureus infection: Potential biomarkers and mechanism.

Staphylococcus aureus is known as a common pathogen that colonizes 30% of healthy humans. Additionally, this bacterium can cause a number of serious infections, that is, endocarditis, bacteremia, pneumonia, wound, skin infections, and tissue abscesses. A variety of cellular and molecular pathways and targets are involved in response against S. aureus. Among them, microRNAs (miRNAs) have crucial roles in response against S. aureus. In this regard, it has been shown that these molecules exert their regulatory roles via modulating a wide range of events, such as inflammatory reactions, host innate, and adaptive immunity. Current works have provided insight into the crucial involvement of miRNAs in immune defense toward Staphylococcal infections. Herein, we highlighted the current findings on the deregulation of different miRNAs in S. aureus-infected cells. Moreover, we summarized the mechanisms and targets of miRNAs in S. aureus infections.

Bacterial co-infections with SARS-CoV-2.

The pandemic coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected millions of people worldwide. To date, there are no proven effective therapies for this virus. Efforts made to develop antiviral strategies for the treatment of COVID-19 are underway. Respiratory viral infections, such as influenza, predispose patients to co-infections and these lead to increased disease severity and mortality. Numerous types of antibiotics such as azithromycin have been employed for the prevention and treatment of bacterial co-infection and secondary bacterial infections in patients with a viral respiratory infection (e.g., SARS-CoV-2). Although antibiotics do not directly affect SARS-CoV-2, viral respiratory infections often result in bacterial pneumonia. It is possible that some patients die from bacterial co-infection rather than virus itself. To date, a considerable number of bacterial strains have been resistant to various antibiotics such as azithromycin, and the overuse could render those or other antibiotics even less effective. Therefore, bacterial co-infection and secondary bacterial infection are considered critical risk factors for the severity and mortality rates of COVID-19. Also, the antibiotic-resistant as a result of overusing must be considered. In this review, we will summarize the bacterial co-infection and secondary bacterial infection in some featured respiratory viral infections, especially COVID-19.

The importance of intracellular bacterial biofilm in infectious diseases.

Various bacterial species, previously known as extracellular pathogens, can reside inside different host cells by adapting to intracellular modes by forming microbial aggregates with similar characteristics to bacterial biofilms. Additionally, bacterial invasion of human cells leads to failure in antibiotic therapy, as most conventional anti-bacterial agents cannot reach intracellular biofilm in normal concentrations. Various studies have shown that bacteria such as uropathogenic Escherichia coli, Pseudomonas aeruginosa, Borrelia burgdorferi,Moraxella catarrhalis, non-typeable Haemophilus influenzae, Streptococcus pneumonia, and group A Streptococci produce biofilm-like structures within the host cells. For the first time in this review, we will describe and discuss the new information about intracellular bacterial biofilm formation and its importance in bacterial infectious diseases.

A hope for ineffective antibiotics to return to treatment: investigating the anti-biofilm potential of melittin alone and in combination with penicillin and oxacillin against multidrug resistant-MRSA and -VRSA.

Background: The emergence and rapid spread of multi-drug resistant (MDR) bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), have posed a significant challenge to the medical community due to their ability to form biofilm and develop resistance to common antibiotics. Traditional antibiotics that were once effective in treating bacterial infections are now becoming increasingly ineffective, leading to severe consequences for patient outcomes. This concerning situation has called for urgent research to explore alternative treatment strategies. Recent studies have shown that antimicrobial peptides (AMPs) hold promise as effective agents against biofilm-associated drug-resistant infections as well as to enhance the efficacy of conventional antibiotics. Accordingly, we aimed to investigate the antimicrobial and antibiofilm effects of melittin AMP, both alone and in combination with penicillin and oxacillin, against biofilm-forming MDR-MRSA and -VRSA. Methods: In this study, we investigated the kinetics of biofilm formation and assessed various parameters related to the antimicrobial and antibiofilm efficacy of melittin and antibiotics, both alone and in combination, against MDR-MRSA and -VRSA. The antimicrobial parameters included the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Fractional Inhibitory Concentration Index (FICi), Fractional Bactericidal Concentration Index (FBCi), and the antibiofilm activity of melittin and antibiotics indicated by the Minimum Biofilm Inhibitory Concentration (MBIC), Minimal Biofilm Eradication Concentration (MBEC), Fractional Biofilm Inhibitory Concentration Index (FBICi), and Fractional Biofilm Eradication Concentration Index (FBECi). Results: The MIC results showed that all S. aureus isolates were resistant to penicillin (≥0.25 µg/mL), and 66% of isolates were resistant to oxacillin. The geometric means of the MIC values for penicillin, oxacillin, and melittin were 19.02, 16, and 1.62 µg/ml, respectively, and the geometric means of the MBC values for penicillin, oxacillin, and melittin were 107.63, 49.35, and 5.45 µg/ml, respectively. The study revealed that the combination indexes of melittin-penicillin and melittin-oxacillin, as determined by FIC values against all isolates, were 0.37 and 0.03, respectively. Additionally, melittin-penicillin and melittin-oxacillin exhibited combination indexes based on FBC values against all isolates at 1.145 and 0.711, respectively. Besides, melittin inhibited the biofilm formation of all S. aureus isolates, with MBIC values ranging from 10 to 1.25 µg/mL, and MBEC values ranging from 40 to 10 µg/mL. Generally, the combination indexes of melittin-penicillin and melittin-oxacillin, determined using FBIC values against all isolates, were 0.23 and 0.177, respectively. Moreover, melittin-penicillin and melittin-oxacillin typically had combination indexes based on FBEC values against all isolates at 5 and 2.97, respectively. Conclusion: In conclusion, our study provides evidence that melittin is effective against both planktonik and biofilm forms of MRSA and VRSA and exhibits significant synergistic effects when combined with antibiotics. These results suggest that melittin and antibiotics could be a potential candidate for further investigation for in vivo infections caused by MDR S. aureus. Furthermore, melittin has the potential to restore the efficacy of penicillin and oxacillin antibiotics in the treatment of MDR infections. Applying AMPs, like melittin, to revive beta-lactam antibiotics against MRSA and VRSA is an innovative approach against antibiotic-resistant bacteria. Further research is needed to optimize dosage and understand melittin mechanism and interactions with beta-lactam antibiotics for successful clinical applications.

Emerging role of microbiota derived outer membrane vesicles to preventive, therapeutic and diagnostic proposes.

The role of gut microbiota and its products in human health and disease is profoundly investigated. The communication between gut microbiota and the host involves a complicated network of signaling pathways via biologically active molecules generated by intestinal microbiota. Some of these molecules could be assembled within nanoparticles known as outer membrane vesicles (OMVs). Recent studies propose that OMVs play a critical role in shaping immune responses, including homeostasis and acute inflammatory responses. Moreover, these OMVs have an immense capacity to be applied in medical research, such as OMV-based vaccines and drug delivery. This review presents a comprehensive overview of emerging knowledge about biogenesis, the role, and application of these bacterial-derived OMVs, including OMV-based vaccines, OMV adjuvants characteristics, OMV vehicles (in conjugated vaccines), cancer immunotherapy, and drug carriers and delivery systems. Moreover, we also highlight the significance of the potential role of these OMVs in diagnosis and therapy.

The Emerging Role of Probiotics and their Derivatives against Biofilm-Producing MRSA: A Scoping Review.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main bacterial pathogens causing chronic infections, mainly because of its capacity to produce biofilm. Biofilm production is one of the underlying strategies for antibacterial drug resistance. Accordingly, preventing and attenuating biofilm production has become an emerging approach to controlling persistent infections. Therefore, this scoping review is aimed at surveying the published literature describing the usage of probiotics and their derivatives against biofilm-producing MRSA. Methods: Updated literature searches were conducted across seven electronic databases including Web of Science, PubMed, Scopus, Cochrane Library, ProQuest, Embase, and Google Scholar to identify all original published articles about probiotics against MRSA. In this regard, studies were summarized and analyzed in the present review. Results: In the reviewed studies, various microorganisms and compounds were used as probiotics as follows: Lactobacillus species (8 studies), Enterococcus species (4 studies), Bacillus species (2 studies), Streptomyces species (2 studies), Saccharomyces cerevisiae (1 study), Corynebacterium accolens (1 study), and Lactococcus lactis derived Nisin (3 studies). Based on our comprehensive search, 21 studies with eligibility criteria were included in the present review including 12 studies on clinical strains, 6 studies on ATCC, 2 studies simultaneously on clinical and standard strains, and finally 1 study on food sample. Conclusions: Our study showed that there was an increasing trend in the number of publications reporting probiotics against biofilm-producing MRSA. The results of this scoping review could use to guide the undertaking of the subsequent systematic reviews. In summary, probiotics with antimicrobial and antibiofilm properties can use as an embedded agent in food products or as a biopharmaceutical in the prevention and treatment of MRSA infections.

Role of microbiota-derived short-chain fatty acids in nervous system disorders.

During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders.

The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune diseases.

Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases.

Molecular Characterization of Hospital- and Community-Acquired Streptococcus agalactiae Isolates among Nonpregnant Adults in Isfahan, Iran.

BACKGROUND: The increasing incidence of Group B Streptococcus (GBS) infection among nonpregnant adults has become of growing clinical and public health concern. The current study investigated the distribution of important virulence determinants and antibiotic susceptibility of GBS isolates causing community acquired (CA) and hospital acquired (HA) infections among nonpregnant adults. MATERIALS AND METHODS: A total of 62 GBS, including 31 CA GBS and 31 HA GBS, were collected from a teaching hospital in Isfahan, Iran. Capsular polysaccharide genotypes (CPS), PI 1, PI 2a, PI 2b, and hypervirulent GBS adhesin (hvgA) virulence genes and antibiotic resistance profiling were determined. RESULTS: There were 19 (30.6%) cases of underlying disease that diabetes mellitus (20.9%) was most common. The rate of multidrug resistant GBS strains was accounted for 29%. Distribution of macrolide resistant phenotypes was as follows: constitutive macrolides, lincosamides, and streptogramin B (MLSB) (15 isolates); inducible resistance to MLSB; and L phenotype (each 5 isolates) and M phenotype (1 isolate). V and Ia serotypes were the most predominant capsular type in HA GBS and CA GBS isolates, respectively. The most frequent pilus types were PI 1, PI 1+PI 2a, PI 1+PI 2b, and PI 2a. PI 1 and PI 1+PI 2a had significantly different distributions between CA and HA GBS isolates. Three CA GBS isolates (9.6%) were positive for hvgA gene that belonged to clonal complex 17/sequence type 17/CPS III/PI 1+PI 2b lineage. CONCLUSION: There was a significant difference in the distribution of PIs among CA GBS and HA GBS isolates in our region.

Correction to: Investigation of antimicrobial susceptibility, class I and II integrons among Pseudomonas aeruginosa isolates from hospitalized patients in Isfahan, Iran.

Following publication of the original article [1], an error was reported in the tables due to a typesetting mistake. Table 3 is presented as a duplicate of Table 2. In this Correction, the correct presentation of Table 3 is shown.

Determination of surface proteins profile, capsular genotyping, and antibiotic susceptibility patterns of Group B Streptococcus isolated from urinary tract infection of Iranian patients.

OBJECTIVES: Group B Streptococcus (GBS) is an important opportunistic bacteria that causes a wide range of infections including neonatal sepsis, meningitis, pneumonia, soft tissue and urinary tract infections (UTI). The aim of this study was to evaluate the antimicrobial susceptibility patterns, surface proteins and capsular types of GBS isolates. RESULTS: 100 of UTI isolates were confirmed as GBS. Antimicrobial susceptibility pattern showed that 95% of GBS isolates were resistant to tetracycline, followed by erythromycin (52%), clindamycin (47%), levofloxacin (9%) and penicillin, cefepime, cefotaxime, and ceftriaxone each with (8%), and vancomycin 1%. Common capsular types were III, Ib, V, II, Ia and IV respectively and the distribution of surface protein genes was as follows: rib (40%), alpha-c (22%), alp2/3 (18%) and epsilon (15%), and alp4 gene was not detected in the isolates. Our findings showed the relationship between capsular types with Alpha-like proteins, as well as reduced sensitivity to antibiotics, so the performance of antibiotic surveillance programs is recommended.

Burden of Clostridium (Clostridioides) difficile Infection among Patients in Western Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Clostridium difficile is the most common causes of hospital-acquired diarrhea affecting particularly hospitalized patients globally. This organism has re-emerged in recent years with significant morbidity and mortality. The present study aimed to estimate the burden of C. difficile infection (CDI) and to acquire information on the overall rates of community- and hospital-acquired CDI in western Asia. METHODS: A systematic literature search was performed to identify articles published from the eight Persian Gulf countries in western Asia including Iran, Iraq, Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates in the electronic databases within Jan of 2000 to Dec of 2017. Then, 20 publications which met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. RESULTS: Twenty studies reported the prevalence of toxigenic strains of C. difficile among patients from Persian Gulf countries, of these the pooled prevalence of CDI was 9% (95% CI: 6.5%-12.5%). Totally, 8 studies showed the prevalence of hospital-acquired CDI, from those studies the prevalence of CDI was estimated 8.4% (95% CI: 4.9%-14.1%). Moreover, 7 studies reported the prevalence of community-acquired CDI, from those studies the prevalence of CDI was estimated 1.8% (95% CI: 1.2%-2.9%). CONCLUSION: The prevalence of CDI in western Asia is lower than southern and eastern region. Moreover, the lower prevalence of community-acquired CDI compared to hospital-acquired CDI, indicate that the source of infection in western Asia is more likely in the hospitals.

Investigation of antimicrobial susceptibility, class I and II integrons among Pseudomonas aeruginosa isolates from hospitalized patients in Isfahan, Iran.

OBJECTIVES: The role of integrons in the transfer of antibiotic resistance is one of the important issues, therefore, this study is aimed to investigate antibiotic resistance pattern and prevalence of class 1 and 2 integrons in P. aeruginosa isolated. RESULTS: Out of 72 confirmed P. aeruginosa isolates, 50% were from ICU patients. Antibacterial susceptibility pattern showed that isolates were most resistant to ceftazidime (76.4%) and colistin was the most effective antibiotic (100%) and molecular analysis of class I and II integrons showed 55.5% and 29.1% of isolates were positive, respectively and the proportions of MDR isolates were significantly higher among integron-positive isolates with 73.6% compared to negative isolates with 22.9%. Our results showed that there was a correlation among class 1 and 2 integrons with MDR P. aeruginosa isolates. According to the importance of integrons in acquisition and dissemination of antibiotics resistance genes, the performance of antibiotic surveillance programs and investigating the role of integrons is recommended to control the spreading of antibiotics resistance genes.