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1.
Structure and Functions of Bacterial Outer Membrane Protein A, A Potential Therapeutic Target for Bacterial Infection.
Guan, Q, Bhowmick, B, Upadhyay, A, Han, Q
Current topics in medicinal chemistry. 2021;(13):1129-1138
Abstract
Outer membrane protein A (OmpA) is a unique outer membrane protein which is abundantly present in the outer membrane of Gram-negative bacteria. OmpA is a transmembrane structural protein with a conserved amino acid sequence among different bacteria. This protein is involved in a number of functions like adhesion, toxicity, invasiveness, and biofilm formation in Gram-negative bacteria. Many studies have proposed that OmpA could be a therapeutic target for bacterial infection. Our review focusses on the studies involving recent development in the structure and functions of OmpA and further discussing its potential as a therapeutic target for bacterial infection.
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2.
Epidermis as a Platform for Bacterial Transmission.
Baquero, F, Saralegui, C, Marcos-Mencía, D, Ballestero, L, Vañó-Galván, S, Moreno-Arrones, ÓM, Del Campo, R
Frontiers in immunology. 2021;:774018
Abstract
The epidermis constitutes a continuous external layer covering the body, offering protection against bacteria, the most abundant living organisms that come into contact with this barrier. The epidermis is heavily colonized by commensal bacterial organisms that help protect against pathogenic bacteria. The highly regulated and dynamic interaction between the epidermis and commensals involves the host's production of nutritional factors promoting bacterial growth together to chemical and immunological bacterial inhibitors. Signal trafficking ensures the system's homeostasis; conditions that favor colonization by pathogens frequently foster commensal growth, thereby increasing the bacterial population size and inducing the skin's antibacterial response, eliminating the pathogens and re-establishing the normal density of commensals. The microecological conditions of the epidermis favors Gram-positive organisms and are unsuitable for long-term Gram-negative colonization. However, the epidermis acts as the most important host-to-host transmission platform for bacteria, including those that colonize human mucous membranes. Bacteria are frequently shared by relatives, partners, and coworkers. The epidermal bacterial transmission platform of healthcare workers and visitors can contaminate hospitalized patients, eventually contributing to cross-infections. Epidermal transmission occurs mostly via the hands and particularly through fingers. The three-dimensional physical structure of the epidermis, particularly the fingertips, which have frictional ridges, multiplies the possibilities for bacterial adhesion and release. Research into the biology of bacterial transmission via the hands is still in its infancy; however, tribology, the science of interacting surfaces in relative motion, including friction, wear and lubrication, will certainly be an important part of it. Experiments on finger-to-finger transmission of microorganisms have shown significant interindividual differences in the ability to transmit microorganisms, presumably due to genetics, age, sex, and the gland density, which determines the physical, chemical, adhesive, nutritional, and immunological status of the epidermal surface. These studies are needed to optimize interventions and strategies for preventing the hand transmission of microorganisms.
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3.
Susceptibility for Some Infectious Diseases in Patients With Diabetes: The Key Role of Glycemia.
Chávez-Reyes, J, Escárcega-González, CE, Chavira-Suárez, E, León-Buitimea, A, Vázquez-León, P, Morones-Ramírez, JR, Villalón, CM, Quintanar-Stephano, A, Marichal-Cancino, BA
Frontiers in public health. 2021;:559595
Abstract
Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (including Chlamydophila pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g., pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.
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4.
The intracellular phase of extracellular respiratory tract bacterial pathogens and its role on pathogen-host interactions during infection.
Lamberti, Y, Surmann, K
Current opinion in infectious diseases. 2021;(3):197-205
Abstract
PURPOSE OF REVIEW An initial intracellular phase of usually extracellular bacterial pathogens displays an important strategy to hide from the host's immune system and antibiotics therapy. It helps the bacteria, including bacterial pathogens of airway diseases, to persist and eventually switch to a typical extracellular infection. Several infectious diseases of the lung are life-threatening and their control is impeded by intracellular persistence of pathogens. Thus, molecular adaptations of the pathogens to this niche but also the host's response and potential targets to interfere are of relevance. Here we discuss examples of historically considered extracellular pathogens of the respiratory airway where the intracellular survival and proliferation is well documented, including infections by Staphylococcus aureus, Bordetella pertussis, Haemophilus influenzae, Pseudomonas aeruginosa, and others. RECENT FINDINGS Current studies focus on bacterial factors contributing to adhesion, iron acquisition, and intracellular survival as well as ways to target them for combatting the bacterial infections. SUMMARY The investigation of common and specific mechanisms of pathogenesis and persistence of these bacteria in the host may contribute to future investigations and identifications of relevant factors and/or bacterial mechanisms to be blocked to treat or improve prevention strategies.
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5.
Scavenging Bacterial Siderophores with Engineered Lipocalin Proteins as an Alternative Antimicrobial Strategy.
Dauner, M, Skerra, A
Chembiochem : a European journal of chemical biology. 2020;(5):601-606
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Abstract
Iron acquisition mediated by siderophores, high-affinity chelators for which bacteria have evolved specific synthesis and uptake mechanisms, plays a crucial role in microbiology and in host-pathogen interactions. In the ongoing fight against bacterial infections, this area has attracted biomedical interest. Beyond several approaches to interfere with siderophore-mediated iron uptake from medicinal and immunochemistry, the development of high-affinity protein scavengers that tightly complex the siderophores produced by pathogenic bacteria has appeared as a novel strategy. Such binding proteins have been engineered based on siderocalin-also known as lipocalin 2-an endogenous human scavenger of enterobactin and bacillibactin that controls the systemic spreading of commensal bacteria such as Escherichia coli. By using combinatorial protein design, siderocalin was reshaped to bind several siderophores from Pseudomonas aeruginosa and, in particular, petrobactin from Bacillus anthracis, none of which is recognized by the natural protein. Such engineered versions of siderocalin effectively suppress the growth of corresponding pathogenic bacteria by depriving them of their iron supply and offer the potential to complement antibiotic therapy in situations of acute or persistent infection.
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Comparison of the effects of Pueraria mirifica gel and of placebo gel on the vaginal microenvironment of postmenopausal women with Genitourinary Syndrome of Menopause (GSM).
Sritonchai, C, Manonai, J, Sophonsritsuk, A, Cherdshewasart, W
Maturitas. 2020;:49-54
Abstract
OBJECTIVE To compare the effects of a 12-week course of 5%Pueraria mirifica gel and placebo gel on the prevalence of bacterial vaginosis, vaginal fungi, vaginal pH, vaginal health index (VHI), and genitourinary symptoms in postmenopausal women. STUDY DESIGN In a randomized, double-blinded, placebo-controlled study (TCTR20160517002), 60 postmenopausal women were randomly assigned to a 12-week course of eitherP. mirifica gel or identical placebo gel. MAIN OUTCOME MEASURE Vaginal Nugent score, fungal culture, pH, VHI, and genitourinary symptoms were evaluated at baseline and after 12 weeks of treatment. RESULTS After 12 weeks of treatment, the proportion of participants with an abnormal Nugent score in the P. mirifica and the placebo groups were 6.7 % (2/30) and 23.3 % (7/30), respectively (p = 0.006). The mean changes in Nugent scores and VHI were significantly higher in the P. mirifica group (p < 0.05). There were no significant decreases in the prevalence of symptoms between the two groups after treatment (p > 0.05). CONCLUSION A 12-week course of treatment with 5 % P. mirifica vaginal gel in postmenopausal women with GSM has been proved to be effective in reducing indicators of bacterial vaginosis compared with placebo gel. Nevertheless, the effect on alleviating genital symptoms was not demonstrated.
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7.
Interventions to reduce contaminated aerosols produced during dental procedures for preventing infectious diseases.
Kumbargere Nagraj, S, Eachempati, P, Paisi, M, Nasser, M, Sivaramakrishnan, G, Verbeek, JH
The Cochrane database of systematic reviews. 2020;(10):CD013686
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Abstract
BACKGROUND Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk. OBJECTIVES To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols. SEARCH METHODS Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication. SELECTION CRITERIA We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility. DATA COLLECTION AND ANALYSIS Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity. MAIN RESULTS We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants). AUTHORS' CONCLUSIONS We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.
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8.
Progress and prospects in the management of bacterial infections and developments in Phytotherapeutic modalities.
Akram, M, Riaz, M, Munir, N, Rasul, A, Daniyal, M, Ali Shah, SM, Shariati, MA, Shaheen, G, Akhtar, N, Parveen, F, et al
Clinical and experimental pharmacology & physiology. 2020;(7):1107-1119
Abstract
The advent of antibiotics revolutionized medical care resulting in significantly reduced mortality and morbidity caused by infectious diseases. However, excessive use of antibiotics has led to the development of antibiotic resistance and indeed, the incidence of multidrug-resistant pathogens is considered as a major disadvantage in medication strategy, which has led the scholar's attention towards innovative antibiotic sources in recent years. Medicinal plants contain a variety of secondary metabolites with a wide range of therapeutic potential against the resistant microbes. Therefore, the aim of this review is to explore the antibacterial potential of traditional herbal medicine against bacterial infections. More than 200 published research articles reporting the therapeutic potential of medicinal plants against drug-resistant microbial infections were searched using different databases such as Google Scholar, Science Direct, PubMed and the Directory of Open Access Journals (DOAJ), etc., with various keywords like medicinal plants having antibacterial activities, antimicrobial potentials, phytotherapy of bacterial infection, etc. Articles were selected related to the efficacious herbs easily available to local populations addressing common pathogens. Various plants such as Artocarpus communis, Rheum emodi, Gentiana lutea L., Cassia fistula L., Rosemarinus officinalis, Argemone maxicana L, Hydrastis canadensis, Citrus aurantifolia, Cymbopogon citrates, Carica papaya, Euphorbia hirta, etc, were found to have significant antibacterial activities. Although herbal preparations have promising potential in the treatment of multidrug-resistant bacterial infection, still more research is required to isolate phytoconstituents, their mechanism of action as well as to find their impacts on the human body.
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Recent Advances in Oral Nano-Antibiotics for Bacterial Infection Therapy.
Wu, ZL, Zhao, J, Xu, R
International journal of nanomedicine. 2020;:9587-9610
Abstract
Bacterial infections are the main infectious diseases and cause of death worldwide. Antibiotics are used to treat various infections ranging from minor to life-threatening ones. The dominant route to administer antibiotics is through oral delivery and subsequent gastrointestinal tract (GIT) absorption. However, the delivery efficiency is limited by many factors such as low drug solubility and/or permeability, gastrointestinal instability, and low antibacterial activity. Nanotechnology has emerged as a novel and efficient tool for targeting drug delivery, and a number of promising nanotherapeutic strategies have been widely explored to overcome these obstacles. In this review, we explore published studies to provide a comprehensive understanding of the recent progress in the area of orally deliverable nano-antibiotic formulations. The first part of this article discusses the functions and underlying mechanisms by which nanomedicines increase the oral absorption of antibiotics. The second part focuses on the classification of oral nano-antibiotics and summarizes the advantages, disadvantages and applications of nanoformulations including lipid, polymer, nanosuspension, carbon nanotubes and mesoporous silica nanoparticles in oral delivery of antibiotics. Lastly, the challenges and future perspective of oral nano-antibiotics for infection disease therapy are discussed. Overall, nanomedicines designed for oral drug delivery system have demonstrated the potential for the improvement and optimization of currently available antibiotic therapies.
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10.
Diet-Microbe-Host Interactions That Affect Gut Mucosal Integrity and Infection Resistance.
Forgie, AJ, Fouhse, JM, Willing, BP
Frontiers in immunology. 2019;:1802
Abstract
The gastrointestinal tract microbiome plays a critical role in regulating host innate and adaptive immune responses against pathogenic bacteria. Disease associated dysbiosis and environmental induced insults, such as antibiotic treatments can lead to increased susceptibility to infection, particularly in a hospital setting. Dietary intervention is the greatest tool available to modify the microbiome and support pathogen resistance. Some dietary components can maintain a healthy disease resistant microbiome, whereas others can contribute to an imbalanced microbial population, impairing intestinal barrier function and immunity. Characterizing the effects of dietary components through the host-microbe axis as it relates to gastrointestinal health is vital to provide evidence-based dietary interventions to mitigate infections. This review will cover the effect of dietary components (carbohydrates, fiber, proteins, fats, polyphenolic compounds, vitamins, and minerals) on intestinal integrity and highlight their ability to modulate host-microbe interactions as to improve pathogen resistance.