Virulence Genes and Biofilm Formation Among Legionella pneumophila Isolates Collected from Hospital Water Sources.

Legionella pneumophila can be transmitted to people, especially immunocompromised patients, via hospital water pipe systems and cause severe pneumonia. The aim of our study was to investigate the presence of major virulence factor genes, ability of biofilms formation, and correlation between presence of Legionella isolates and temperature, pH, and residual chlorine of water. Hundred water samples were collected from nine hospitals in Tehran, Iran. Temperature, pH, and residual chlorine were determined during sampling. Different virulence genes and the ability to form biofilms were subsequently analyzed among the L. pneumophila isolates. Results showed that 12 (12%) samples were positive in culture method and all of the isolates were positive as L. pneumophila species (mip). A correlation was found between Legionella culture positivity and temperature and pH of water, but there was no significant correlation between residual chlorine of water samples and the presence of Legionella. The isolation of Legionella rate in summer and spring was higher than winter and autumn. Twelve (100%) isolates were positive for mip genes, 9 (75%) for dot genes, 8 (66.66%) for hsp, 6 (50%) for lvh, and 4 (33.33%) for rtx. All of the isolates displayed strong ability for biofilm production every three days. Two of these isolates (16.6%) displayed weak ability to form biofilm on the first day of incubation. This study revealed that water sources in hospitals were colonized by virulent Legionella and should be continuously monitored to avoid elevated concentrations of Legionella with visible biofilm formation.

Upregulation of pmrA, pmrB, pmrC, phoQ, phoP, and arnT genes contributing to resistance to colistin in superbug Klebsiella pneumoniae isolates from human clinical samples in Tehran, Iran.

Background: Antibiotic resistance in Klebsiella pneumoniae isolates, particularly resistance to colistin, has become a growing concern. This study seeks to investigate the upregulation of specific genes (pmrA, pmrB, pmrC, phoQ, phoP, and arnT) that contribute to colistin resistance in K. pneumoniae isolates collected from human clinical samples in Tehran, Iran. Methods: Thirty eight K. pneumoniae isolates were obtained and subjected to antibiotic susceptibility testing, as well as evaluation for phenotypic AmpC and ESBL production according to CLSI guidelines. The investigation of antibiotic resistance genes was conducted using polymerase chain reaction (PCR), whereas the quantification of colistin resistance related genes expressions was performed via Real-Time PCR. Results: The highest and lowest antibiotics resistance were observed for cefotaxime 33 (86.8%) and minocycline 8 (21.1%), respectively. Twenty-four (63.2%) and 31 (81.6%) isolates carried AmpC and ESBLs, respectively. Also, antibiotic resistance genes containing blaNDM, blaIMP, blaVIM, blaSHV, blaTEM, blaCTXM, qnrA, qnrB, qnrS, and aac(6')-Ib were detected in K. pneumoniae isolates. Only 5 (13.1%) isolates were resistant to colistin and the MIC range of these isolates was between 4 and 64 µg ml-1. Upregulation of the pmrA, pmrB, pmrC, phoQ, phoP, and arnT genes was observed in colistin-resistant isolates. The colistin-resistant isolates were found to possess a simultaneous presence of ESBLs, AmpC, fluoroquinolone, aminoglycoside, and carbapenem resistant genes. Conclusions: This study reveals escalating antibiotic resistance in K. pneumoniae, with notable coexistence of various resistance traits, emphasizing the need for vigilant surveillance and innovative interventions.

Phage therapy as a glimmer of hope in the fight against the recurrence or emergence of surgical site bacterial infections.

PURPOSE: Over the last decade, surgery rates have risen alarmingly, and surgical-site infections are expanding these concerns. In spite of advances in infection control practices, surgical infections continue to be a significant cause of death, prolonged hospitalization, and morbidity. As well as the presence of bacterial infections and their antibiotic resistance, biofilm formation is one of the challenges in the treatment of surgical wounds. METHODS: This review article was based on published studies on inpatients and laboratory animals receiving phage therapy for surgical wounds, phage therapy for tissue and bone infections treated with surgery to prevent recurrence, antibiotic-resistant wound infections treated with phage therapy, and biofilm-involved surgical wounds treated with phage therapy which were searched without date restrictions. RESULTS: It has been shown in this review article that phage therapy can be used to treat surgical-site infections in patients and animals, eliminate biofilms at the surgical site, prevent infection recurrence in wounds that have been operated on, and eradicate antibiotic-resistant infections in surgical wounds, including multi-drug resistance (MDR), extensively drug resistance (XDR), and pan-drug resistance (PDR). A cocktail of phages and antibiotics can also reduce surgical-site infections more effectively than phages alone. CONCLUSION: In light of these encouraging results, clinical trials and research with phages will continue in the near future to treat surgical-site infections, biofilm removal, and antibiotic-resistant wounds, all of which could be used to prescribe phages as an alternative to antibiotics.

Engineered phage enzymes against drug-resistant pathogens: a review on advances and applications.

In recent decades, the expansion of multi and extensively drug-resistant (MDR and XDR) bacteria has reached an alarming rate, causing serious health concerns. Infections caused by drug-resistant bacteria have been associated with morbidity and mortality, making tackling bacterial resistance an urgent and unmet challenge that needs to be addressed properly. Endolysins are phage-encoded enzymes that can specifically degrade the bacterial cell wall and lead to bacterial death. There is remarkable evidence that corroborates the unique ability of endolysins to rapidly digest the peptidoglycan particular bonds externally without the assistance of phage. Thus, their modulation in therapeutic approaches has opened new options for therapeutic applications in the fight against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology areas. The use of genetically engineered phage enzymes (EPE) promises to generate endolysin variants with unique properties for prophylactic and therapeutic applications. These approaches have gained momentum to accelerate basic as well as translational phage research and the potential development of therapeutics in the near future. This review will focus on the novel knowledge into EPE and demonstrate that EPE has far better performance than natural endolysins and phages in dealing with antibiotic-resistant infections. Therefore, it provides essential information for clinical trials involving EPE.

The therapeutic effect of engineered phage, derived protein and enzymes against superbug bacteria.

Defending against antibiotic-resistant infections is similar to fighting a war with limited ammunition. As the new century unfolded, antibiotic resistance became a significant concern. In spite of the fact that phage treatment has been used as an effective means of fighting infections for more than a century, researchers have had to overcome many challenges of superbug bacteria by manipulating phages and producing engineered enzymes. New enzymes and phages with enhanced properties have a significant impact on the ability to fight antibiotic-resistant infections, which is considered a window of hope for the future. This review, therefore, illustrates not only the challenges caused by antibiotic resistance and superbug bacteria but also the engineered enzymes and phages that are being developed to solve these issues. Our study found that engineered phages, phage proteins, and enzymes can be effective in treating superbug bacteria and destroying the biofilm caused by them. Combining these engineered compounds with other antimicrobial substances can increase their effectiveness against antibiotic-resistant bacteria. Therefore, engineered phages, proteins, and enzymes can be used as a substitute for antibiotics or in combination with antibiotics to treat patients with superbug infections in the future.

Perturbations in Microbiota Composition as a Novel Mediator in Neuropsychiatric, Neurological and Mental Disorders: Preventive and Therapeutic Complementary Therapies to Balance the Change.

Although microbiology and neurology are separate disciplines, they are linked to some infectious and neurological diseases. Today, microbiome is considered as one of the biomarkers of health by many researchers. This has led to the association of microbiome changes with many neurological diseases. The natural microbiota has many beneficial properties. If disrupted and altered, it can lead to irreversible complications and many neurological diseases. Therefore, according to previous studies, some preventive and therapeutic complementary therapies can prevent or restore microbiome dysbiosis and inflammation in the nervous system. With our current perception of the microbiological basis for different neurological disorders, both aspects of drug treatment and control of perturbations of the microbiome should be considered, and targeting them simultaneously will likely help to attain favorable results.

The effect of bacterial composition shifts in the oral microbiota on Alzheimer's disease.

Alzheimer's disease (AD), a neurological disorder, despite significant advances in medical science, has not yet been definitively cured, and the exact causes of the disease remain unclear. Due to the importance of AD in the clinic, large expenses are spent annually to deal with this neurological disorder, and neurologists warn of an alarm to increase this disease in the elderly people in the near future. It has been believed that microbiota dysbiosis lead to Alzheimer's as a multi-step disease. In this regard, the presence of footprints of perturbations in the oral microbiome and the predominance of pathogenic bacteria and their effect on the nervous system especially AD is a very interesting topic that has been considered by researchers in the last decade. Some studies have looked at the mechanisms by which oral microbiota cause AD. However, many aspects of this interaction are still unclear as to how oral microbiota composition can contribute to this disease. Understanding this interaction requires extensive collaboration by interdisciplinary researchers to explore all aspects of the issue. So, in this review has attempted to give the mechanisms of shift of oral microbiota in AD in order to reveals the link between microbiota composition and this disease with the help of researchers from different fields.

Rescuing humanity by antimicrobial peptides against colistin-resistant bacteria.

It has been about a century since the discovery of the first antibiotic, and during this period, several antibiotics were produced and marketed. The production of high-potency antibiotics against infections led to victories, but these victories were temporary. Overuse and misuse of antibiotics have continued to the point that humanity today is almost helpless in the fight against infection. Researchers have predicted that by the middle of the new century, there will be a dark period after the production of antibiotics that doctors will encounter antibiotic-resistant infections for which there is no cure. Accordingly, researchers are looking for new materials with antimicrobial properties that will strengthen their ammunition to fight antibiotic-resistant infections. One of the most important alternatives to antibiotics introduced in the last three decades is antimicrobial peptides (AMPs), which affect a wide range of microbes. Due to their different antimicrobial properties from antibiotics, AMPs can fight and kill MDR, XDR, and colistin-resistant bacteria through a variety of mechanisms. Therefore, in this study, we intend to use the latest studies to give a complete description of AMPs, the importance of colistin-resistant bacteria, and their resistance mechanisms, and represent impact of AMPs on colistin-resistant bacteria. KEY POINTS: • AMPs as limited options to kill colistin-resistant bacteria. • Challenge of antibiotics resistance, colistin resistance, and mechanisms. • What is AMPs in the war with colistin-resistant bacteria?

Bacteriophage as a Novel Therapeutic Weapon for Killing Colistin-Resistant Multi-Drug-Resistant and Extensively Drug-Resistant Gram-Negative Bacteria.

Colistin-resistant multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria are highly lethal and many researchers have tried hard to combat these microorganisms around the world. Infections caused by these bacteria are resistant to the last resort of antibiotic therapy and have posed a major challenge in clinical and public health. Since the production of new antibiotics is very expensive and also very slow compared to the increasing rate of antibiotic resistance, researchers are suggesting the use of natural substances with high antibacterial potential. Bacteriophages are one of the most effective therapeutic measures that are known to exist for use for incurable and highly resistant infections. Phages are highly taken into consideration due to the lack of side effects, potential spread to various body organs, distinct modes of action from antibiotics, and proliferation at the site of infection. Although the effects of phages on MDR and XDR bacteria have been demonstrated in various studies, only a few have investigated the effect of phage therapy on colistin-resistant isolates. Therefore, in this review, we discuss the problems caused by colistin-resistant MDR and XDR bacteria in the clinics, explain the different mechanisms associated with colistin resistance, introduce bacteriophage therapy as a powerful remedy, and finally present new studies that have used bacteriophages against colistin-resistant isolates.

The association of Chlamydia pneumoniae infection with atherosclerosis: Review and update of in vitro and animal studies.

Previous studies have tended to relate Chlamydia pneumoniae (Cpn) infection to atherosclerosis. However, while serological studies have mostly reinforced this hypothesis, inconsistent and even contradictory findings have been reported in various researches. Recent papers have pointed to the significance of Cpn in atherosclerotic lesions, which are regarded as the initiator and cause of chronic inflammation. This bacterium develops atherosclerosis by phenotypic changes in vascular smooth muscle cells, dysregulation of endothelin-1 in the vascular wall, and releasing pro-inflammatory cytokines from Toll-like receptor-2 (TLR2). Furthermore, Cpn infection, particularly under hyperlipidemic conditions, enhances monocyte adhesion to endothelium; changes the physiology of the host, e.g., cholesterol homeostasis; and activates the Low-density lipoprotein (LDL) receptor, which is the initial step in atherogenesis. On the other hand, it has been reported that Cpn, even without the immune system of the host, has the ability to stimulate arterial thickening. Moreover, there is evidence that Cpn can increase the impact of the classical risk factors such as hyperlipidemia, pro-inflammatory cytokines, and smoking for atherosclerosis. Furthermore, animal studies have shown that Cpn infection can induce atherosclerotic, which alongside hyperlipidemia is a co-risk factor for cardiovascular disease. Although the exact link between Cpn and atherosclerosis has not been determined yet, previous studies have reported possible mechanisms of pathogenesis for this bacterium. Accordingly, investigating the exact role of this infection in causing atherosclerosis may be helpful in controlling the disease.

Helicobacter pylori Biofilm and New Strategies to Combat it.

Helicobacter pylori, the most frequent pathogen worldwide that colonizes around 50% of the world's population, causes important diseases such as gastric adenocarcinoma, chronic gastritis, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In recent years, various studies have reported that H. pylori biofilm may be one of the critical barriers to the eradication of this bacterial infection. Biofilms inhibit the penetration of antibiotics, increase the expression of efflux pumps and mutations, multiple therapeutic failures, and chronic infections. Nanoparticles and natural products can demolish H. pylori biofilm by destroying the outer layers and inhibiting the initial binding of bacteria. Also, the use of combination therapies destroying extracellular polymeric substances decreases coccoid forms of bacteria and degrading polysaccharides in the outer matrix that lead to an increase in the permeability and performance of antibiotics. Different probiotics, antimicrobial peptides, chemical substances, and polysaccharides by inhibiting adhesion and colonization of H. pylori can prevent biofilm formation by this bacterium. Of note, many of the above are applicable to acidic pH and can be used to treat gastritis. Therefore, H. pylori biofilm may be one of the major causes of failure to eradication of infections caused by this bacterium, and antibiotics are not capable of destroying the biofilm. Thus, it is necessary to use new strategies to prevent recurrent and chronic infections by inhibiting biofilm formation.

Global prevalence and distribution of vancomycin resistant, vancomycin intermediate and heterogeneously vancomycin intermediate Staphylococcus aureus clinical isolates: a systematic review and meta-analysis.

Vancomycin-resistant Staphylococcus aureus (VRSA), Vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) are subject to vancomycin treatment failure. The aim of the present study was to determine their precise prevalence and investigate prevalence variability depending on different years and locations. Several international databases including Medline (PubMed), Embase and Web of Sciences were searched (data from 1997 to 2019) to identify studies that addressed the prevalence of VRSA, VISA and hVISA among human clinical isolates around the world. Subgroup analyses and meta-regression were conducted to indicate potential source of variation. Publication bias was assessed using Egger's test. Statistical analyses were conducted using STATA software (version 14.0). Data analysis showed that VRSA, VISA and hVISA isolates were reported in 23, 50 and 82 studies, with an overall prevalence of 1.5% among 5855 S. aureus isolates, 1.7% among 22,277 strains and 4.6% among 47,721 strains, respectively. The overall prevalence of VRSA, VISA, and hVISA before 2010 was 1.2%, 1.2%, and 4%, respectively, while their prevalence after this year has reached 2.4%, 4.3%, and 5.3%. The results of this study showed that the frequency of VRSA, VISA and hVISA after 2010 represent a 2.0, 3.6 and 1.3-fold increase over prior years. In a subgroup analysis of different strain origins, the highest frequency of VRSA (3.6%) and hVISA (5.2%) was encountered in the USA while VISA (2.1%) was more prevalent in Asia. Meta-regression analysis showed significant increasing of VISA prevalence in recent years (p value ≤ 0.05). Based on the results of case reports (which were not included in the calculations mentioned above), the numbers of VRSA, VISA and hVISA isolates were 12, 24 and 14, respectively, among different continents. Since the prevalence of VRSA, VISA and hVISA has been increasing in recent years (especially in the Asian and American continents), rigorous monitoring of vancomycin treatment, it's the therapeutic response and the definition of appropriate control guidelines depending on geographical regions is highly recommended and essential to prevent the further spread of vancomycin-resistant S. aureus.

Ramadan Fasting During the COVID-19 Pandemic; Observance of Health, Nutrition and Exercise Criteria for Improving the Immune System.

Fasting is one of the religious rituals of Muslims worldwide who refrain from eating foods and liquids every year during Ramadan. This year (2020), Ramadan is very different from previous years due to the outbreak of a terrible microscopic giant called coronavirus disease 2019 (COVID-19). The pandemic COVID-19 has made Ramadan very important this year because the virus has infected millions of people around the world and killed thousands, especially people with immunodeficiency. In dealing with COVID-19, maintaining good hygiene and supporting the immune system are effective, preventive approaches. Moderate exercise training and proper nutrition are the most important factors to support immune function. Lack of facilities, poor health and many traditions that lead to public community gatherings have made many Islamic countries susceptible to this dangerous virus. In such an unprecedented situation, there are many Muslims who doubt whether they can fast or not. Therefore, the proposal of usable exercise programs and effective nutritional strategies is imperative. In this study, we will look at the proposed health effects of fasting and its impact on the immune system, the effects of Ramadan intermittent fasting on resting values and responses of immunological/antioxidant biomarkers in elite and recreational athletes, together with the important health, nutrition, and exercise advice that fasting people need to follow in the event of a COVID-19 outbreak.

The effects of probiotics on reducing the colorectal cancer surgery complications: A periodic review during 2007-2017.

BACKGROUND & AIMS: To assess the effects of pro-/synbiotic treatment on patients with colorectal cancer (CRC), a systematic review was conducted on randomized controlled trials. METHODS: International databanks (ISI Web of Science, PubMed, Scopus, and Google Scholar) were searched from January 2007 to December 2017 using the following keywords: 'colorectal cancer' and 'probiotics'. The search was restricted to original articles published in English. Reference lists of all related studies were also reviewed to find other relevant publications. The statistical analysis was performed using SPSS software version 18.0 (IBM, NY, USA). Also, p < .05 was regarded as statistically significant. RESULTS: A total of 21 clinical trials were retrieved, involving 1831 patients subjected to elective colorectal surgery. The studies included in this review have investigated the effects of probiotics on different aspects of colorectal cancer treatment (p < .05). According to the present study results, probiotics could significantly decrease inflammatory factors, chemotherapy side effects, severe diarrhea, postoperative infectious complications, and duration of antibiotic therapy; shift fecal microbiota in favor of Actinobacteria; and change the tumor tissue microbiota (p < .05). CONCLUSION: Based on the present review, the preoperative use of pro-/synbiotics as prophylaxis for patients with CRC could improve clinical outcomes. More detailed data about the types of probiotic species and the optimal consumption dose of pro-/synbiotics should be taken in to account in future meta-analysis reviews.