Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review.

Background: Diabetes has evolved into a worldwide public health issue. One of the most serious complications of diabetes is diabetic foot ulcer (DFU), which frequently creates a significant financial strain on patients and lowers their quality of life. Up until now, there has been no curative therapy for DFU, only symptomatic relief or an interruption in the disease's progression. Recent studies have focused attention on mesenchymal stem cells (MSCs), which provide innovative and potential treatment candidates for several illnesses as they can differentiate into various cell types. They are mostly extracted from the placenta, adipose tissue, umbilical cord (UC), and bone marrow (BM). Regardless of their origin, they show comparable features and small deviations. Our goal is to investigate MSCs' therapeutic effects, application obstacles, and patient benefit strategies for DFU therapy. Methodology: A comprehensive search was conducted using specific keywords relating to DFU, MSCs, and connected topics in the databases of Medline, Scopus, Web of Science, and PubMed. The main focus of the selection criteria was on English-language literature that explored the relationship between DFU, MSCs, and related factors. Results and Discussion: Numerous studies are being conducted and have demonstrated that MSCs can induce re-epithelialization and angiogenesis, decrease inflammation, contribute to immunological modulation, and subsequently promote DFU healing, making them a promising approach to treating DFU. This review article provides a general snapshot of DFU (including clinical presentation, risk factors and etiopathogenesis, and conventional treatment) and discusses the clinical progress of MSCs in the management of DFU, taking into consideration the side effects and challenges during the application of MSCs and how to overcome these challenges to achieve maximum benefits. Conclusion: The incorporation of MSCs in the management of DFU highlights their potential as a feasible therapeutic strategy. Establishing a comprehensive understanding of the complex relationship between DFU pathophysiology, MSC therapies, and related obstacles is essential for optimizing therapy outcomes and maximizing patient benefits.

Characterization of antibiotic and disinfectant susceptibility in biofilm-forming Acinetobacter baumannii: A focus on environmental isolates.

The clinical role of Acinetobacter baumannii has been highlighted in numerous infectious syndromes with a high mortality rate, due to the high prevalence of multidrug-resistant (MDR) isolates. The treatment and eradication of this pathogen is hindered by biofilm-formation, providing protection from noxious environmental factors and antimicrobials. The aim of this study was to assess the antibiotic susceptibility, antiseptic susceptibility and biofilm-forming capacity using phenotypic methods in environmental A. baumannii isolates. One hundred and fourteen (n = 114) isolates were collected, originating from various environmental sources and geographical regions. Antimicrobial susceptibility testing was carried out using the disk diffusion method, while antiseptic susceptibility was performed using the agar dilution method. Determination of biofilm-forming capacity was carried out using a microtiter-plate based method. Resistance in environmental A. baumannii isolates were highest for ciprofloxacin (64.03%, n = 73), levofloxacin (62.18%, n = 71) and trimethoprim-sulfamethoxazole (61.40%, n = 70), while lowest for colistin (1.75%, n = 2). Efflux pump overexpression was seen in 48.25% of isolates (n = 55), 49.12% (n = 56) were classified as MDR. 6.14% (n = 7), 9.65% (n = 11), 24.65% (n = 28) and 59.65% (n = 68) of isolates were non-biofilm producers, weak, medium, and strong biofilm producers, respectively. No significant differences were observed between non-MDR vs. MDR isolates regarding their distribution of biofilm-producers (P = 0.655). The MIC ranges for the tested antiseptics were as follows: benzalkonium chloride 16-128 µg mL-1, chlorhexidine digluconate 4-128 µg mL-1, formaldehyde 64-256 µg mL-1 and triclosan 2-16 µg mL-1, respectively. The conscientious use of antiseptics, together with periodic surveillance, is essential to curb the spread of these bacteria, and to maintain current infection prevention capabilities.

Sequencing analysis and efficient biodiesel production by lipase from Pseudomonas aeruginosa.

BACKGROUND: Recently, lipase processing for biodiesel production has shown a global increase as it is considered a potential alternative clean-fuel source. The current study's objective is to investigate of lipolytic activity of lipase produced from different strains of Pseudomonas aeruginosa (P. aeruginosa) in biodiesel production using edible plant oils. The goal is to develop an efficient and cost-effective method for producing inexpensive and environmentally friendly biodiesel. METHODS AND RESULTS: Four P. aeruginosa isolates were obtained from different environmental sources (soil), phenotypically identified, and it was confirmed by the PCR detection of the 16SrRNA gene. The isolated P. aeruginosa strains were screened for lipase production, and the recovered lipase was purified. Besides, the lipase (lip) gene was detected by PCR, and the purified PCR products were sequenced and analyzed. The production of biofuel was conducted using gas chromatography among tested oils. It was found that castor oil was the best one that enhances lipase production in-vitro.

Meat and meat products as potential sources of emerging MDR Bacillus cereus: groEL gene sequencing, toxigenic and antimicrobial resistance.

BACKGROUND: Bacillus cereus is implicated in severe foodborne infection in humans. This study intended to assess the occurrence, groEL gene sequencing, biofilm production, and resistance profiles of emerged multidrug resistant (MDR) B. cereus in meat and meat product samples. Moreover, this work highlights the virulence and toxigenic genes (hblABCD complex, nheABC complex, cytK, ces, and pc-plc) and antimicrobial resistance genes (bla1, tetA, bla2, tetB, and ermA). METHODS: Consequently, 200 samples (sausage, minced meat, luncheon, beef meat, and liver; n = 40 for each) were indiscriminately collected from commercial supermarkets in Port Said Province, Egypt, from March to May 2021. Subsequently, food samples were bacteriologically examined. The obtained isolates were tested for groEL gene sequence analysis, antibiotic susceptibility, biofilm production, and PCR screening of toxigenic and resistance genes. RESULTS: The overall prevalence of B. cereus among the inspected food samples was 21%, where the highest predominance was detected in minced meat (42.5%), followed by beef meat (30%). The phylogenetic analysis of the groEL gene exposed that the examined B. cereus strain disclosed a notable genetic identity with other strains from the USA and China. Moreover, the obtained B. cereus strains revealed ß-hemolytic activity, and 88.1% of the recovered strains tested positive for biofilm production. PCR evidenced that the obtained B. cereus strains usually inherited the nhe complex genes (nheA and nheC: 100%, and nheB: 83.3%), followed by cytK (76.2%), hbl complex (hblC and hblD: 59.5%, hblB: 16.6%, and hblA: 11.9%), ces (54.7%), and pc-plc (30.9%) virulence genes. Likewise, 42.9% of the examined B. cereus strains were MDR to six antimicrobial classes and encoded bla1, bla2, ermA, and tetA genes. CONCLUSION: In summary, this study highlights the presence of MDR B. cereus in meat and meat products, posing a significant public health risk. The contamination by B. cereus is common in minced meat and beef meat. The molecular assay is a reliable fundamental tool for screening emerging MDR B. cereus strains in meat and meat products.

The secrets of environmental Pseudomonas aeruginosa in slaughterhouses: Antibiogram profile, virulence, and antibiotic resistance genes.

Environmental pollution is a serious problem that can cause sicknesses, fatality, and biological contaminants such as bacteria, which can trigger allergic reactions and infectious illnesses. There is also evidence that environmental pollutants can have an impact on the gut microbiome and contribute to the development of various mental health and metabolic disorders. This study aimed to study the antibiotic resistance and virulence potential of environmental Pseudomonas aeruginosa (P. aeruginosa) isolates in slaughterhouses. A total of 100 samples were collected from different slaughterhouse tools. The samples were identified by cultural and biochemical tests and confirmed by the VITEK 2 system. P. aeruginosa isolates were further confirmed by CHROMagar™ Pseudomonas and genetically by rpsL gene analysis. Molecular screening of virulence genes (fimH, papC, lasB, rhlI, lasI, csgA, toxA, and hly) and antibiotic resistance genes (blaCTX-M, blaAmpC, blaSHV, blaNDM, IMP-1, aac(6')-Ib-, ant(4')IIb, mexY, TEM, tetA, and qnrB) by PCR and testing the antibiotic sensitivity, biofilm formation, and production of pigments, and hemolysin were carried out in all isolated strains. A total of 62 isolates were identified as P. aeruginosa. All P. aeruginosa isolates were multidrug-resistant and most of them have multiple resistant genes. blaCTX-M gene was detected in all strains; 23 (37.1%) strains have the ability for biofilm formation, 33 strains had virulence genes, and 26 isolates from them have more than one virulence genes. There should be probably 60 (96.8%) P. aeruginosa strains that produce pyocyanin pigment. Slaughterhouse tools are sources for multidrug-resistant and virulent pathogenic microorganisms which are a serious health problem. Low-hygienic slaughterhouses could be a reservoir for resistance and virulence genes which could then be transferred to other pathogens.

Phage Therapy, a Salvage Treatment for Multidrug-Resistant Bacteria Causing Infective Endocarditis.

Infective endocarditis (IE) is defined as an infection of the endocardium, or inner surface of the heart, most frequently affecting the heart valves or implanted cardiac devices. Despite its rarity, it has a high rate of morbidity and mortality. IE generally occurs when bacteria, fungi, or other germs from another part of the body, such as the mouth, spread through the bloodstream and attach to damaged areas in the heart. The epidemiology of IE has changed as a consequence of aging and the usage of implantable cardiac devices and heart valves. The right therapeutic routes must be assessed to lower complication and fatality rates, so this requires early clinical suspicion and a fast diagnosis. It is urgently necessary to create new and efficient medicines to combat multidrug-resistant bacterial (MDR) infections because of the increasing threat of antibiotic resistance on a worldwide scale. MDR bacteria that cause IE can be treated using phages rather than antibiotics to combat MDR bacterial strains. This review will illustrate how phage therapy began and how it is considered a powerful potential candidate for the treatment of MDR bacteria that cause IE. Furthermore, it gives a brief about all reported clinical trials that demonstrated the promising effect of phage therapy in combating resistant bacterial strains that cause IE and how it will become a hope in future medicine.

Global genomic epidemiology of chromosomally mediated non-enzymatic carbapenem resistance in Acinetobacter baumannii: on the way to predict and modify resistance.

Introduction: Although carbapenemases are frequently reported in resistant A. baumannii clinical isolates, other chromosomally mediated elements of resistance that are considered essential are frequently underestimated. Having a wide substrate range, multidrug efflux pumps frequently underlie antibiotic treatment failure. Recognizing and exploiting variations in multidrug efflux pumps and penicillin-binding proteins (PBPs) is an essential approach in new antibiotic drug discovery and engineering to meet the growing challenge of multidrug-resistant Gram-negative bacteria. Methods: A total of 980 whole genome sequences of A. baumannii were analyzed. Nucleotide sequences for the genes studied were queried against a custom database of FASTA sequences using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) system. The correlation between different variants and carbapenem Minimum Inhibitory Concentrations (MICs) was studied. PROVEAN and I-Mutant predictor suites were used to predict the effect of the studied amino acid substitutions on protein function and protein stability. Both PsiPred and FUpred were used for domain and secondary structure prediction. Phylogenetic reconstruction was performed using SANS serif and then visualized using iTOL and Phandango. Results: Exhibiting the highest detection rate, AdeB codes for an important efflux-pump structural protein. T48V, T584I, and P660Q were important variants identified in the AdeB-predicted multidrug efflux transporter pore domains. These can act as probable targets for designing new efflux-pump inhibitors. Each of AdeC Q239L and AdeS D167N can also act as probable targets for restoring carbapenem susceptibility. Membrane proteins appear to have lower predictive potential than efflux pump-related changes. OprB and OprD changes show a greater effect than OmpA, OmpW, Omp33, and CarO changes on carbapenem susceptibility. Functional and statistical evidence make the variants T636A and S382N at PBP1a good markers for imipenem susceptibility and potential important drug targets that can modify imipenem resistance. In addition, PBP3_370, PBP1a_T636A, and PBP1a_S382N may act as potential drug targets that can be exploited to counteract imipenem resistance. Conclusion: The study presents a comprehensive epidemiologic and statistical analysis of potential membrane proteins and efflux-pump variants related to carbapenem susceptibility in A. baumannii, shedding light on their clinical utility as diagnostic markers and treatment modification targets for more focused studies of candidate elements.

Gallibacterium anatis infection in poultry: a comprehensive review.

Gallibacterium anatis (G. anatis), a member of the Pasteurellaceae family, normally inhabits the upper respiratory and lower genital tracts of poultry. However, under certain circumstances of immunosuppression, co-infection (especially with Escherichia coli or Mycoplasma), or various stressors, G. anatis caused respiratory, reproductive, and systemic diseases. Infection with G. anatis has emerged in different countries worldwide. The bacterium affects mainly chickens; however, other species of domestic and wild birds may get infected. Horizontal, vertical, and venereal routes of G. anatis infection have been reported. The pathogenicity of G. anatis is principally related to the presence of some essential virulence factors such as Gallibacterium toxin A, fimbriae, haemagglutinin, outer membrane vesicles, capsule, biofilms, and protease. The clinical picture of G. anatis infection is mainly represented as tracheitis, oophoritis, salpingitis, and peritonitis, while other lesions may be noted in cases of concomitant infection. Control of such infection depends mainly on applying biosecurity measures and vaccination. The antimicrobial sensitivity test is necessary for the correct treatment of G. anatis. However, the development of multiple drug resistance is common. This review article sheds light on G. anatis regarding history, susceptibility, dissemination, virulence factors, pathogenesis, clinical picture, diagnosis, and control measures.

Resistance profiles, virulence and antimicrobial resistance genes of XDR S. Enteritidis and S. Typhimurium.

Avian salmonellosis is concomitant with high financial crises in the poultry industry as well as food-borne illness in man. The present study is designed to investigate the emergence of Salmonella Enteritidis and Salmonella Typhimurium in diseased broilers, resistance profiles, and monitoring virulence and antibiotic resistance genes. Consequently, 450 samples (cloacal swabs, liver, and spleen) were collected from 150 diseased birds from different farms in Giza Governorate, Egypt. Subsequently, the bacteriological examination was done. Afterward, the obtained Salmonella isolates were tested for serogrouping, antibiogram, PCR monitoring of virulence (invA, stn, hilA, and pefA), and antimicrobial resistance genes (blaTEM, blaCTX-M, blaNDM, ermA, sul1, tetA, and aadA1). The total prevalence of Salmonella in the examined diseased broilers was 9.3%, and the highest prevalence was noticed in cloacal swabs. Among the recovered Salmonella isolates (n = 35), 20 serovars were recognized as S. Enteritidis and 15 serovars were identified as S. Typhimurium. Almost 60% of the retrieved S. Enteritidis serovars were extensively drug-resistant (XDR) to seven antimicrobial classes and inherited sul1, blaTEM, tetA, blaCTX-M, ereA, and aadA1 genes. Likewise, 25% of the recovered S. Enteritidis serovars were multidrug-resistant (MDR) to six classes and have sul1, blaTEM, tetA, blaCTX-M, and ereA resistance genes. Also, 66.7% of the retrieved S. Typhimurium serovars were XDR to seven classes and have sul1, blaTEM, tetA, blaCTX-M, ereA, and aadA1 genes. Succinctly, this report underlined the reemergence of XDR S. Typhimurium and S. Enteritidis in broiler chickens. Meropenem and norfloxacin exposed a hopeful antimicrobial activity toward the re-emerging XDR S. Typhimurium and S. Enteritidis in broilers. Moreover, the recurrence of these XDR Salmonella strains poses a potential public health threat.

COVID-19 associated Mucormycosis among ICU patients: risk factors, control, and challenges.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is still difficult to be controlled. The spread of this virus and the emergence of new variants are considered a great challenge worldwide. Disturbance in infection control guidelines implementation, use of steroids, antibiotics, hospital crowdedness, and repeated use of oxygen masks during the management of critically ill COVID-19 patients lead to an increase in the rate of opportunistic infections. So, patients need to fight both the virus with its different variants and opportunistic pathogens including bacteria and fungi especially patients with diabetes mellitus, malignancy, or those who undergo hemodialysis and receive deferoxamine. During the pandemic, many cases of Mucormycosis associated with COVID-19 infection were observed in many countries. In this review, we discuss risk factors that increase the chance of infection by opportunistic pathogens, especially fungal pathogens, recent challenges, and control measures.

Pangenome analysis of Corynebacterium striatum: insights into a neglected multidrug-resistant pathogen.

BACKGROUND: Over the past two decades, Corynebacterium striatum has been increasingly isolated from clinical cultures with most isolates showing increased antimicrobial resistance (AMR) to last resort agents. Advances in the field of pan genomics would facilitate the understanding of the clinical significance of such bacterial species previously thought to be among commensals paving the way for identifying new drug targets and control strategies. METHODS: We constructed a pan-genome using 310 genome sequences of C. striatum. Pan-genome analysis was performed using three tools including Roary, PIRATE, and PEPPAN. AMR genes and virulence factors have been studied in relation to core genome phylogeny. Genomic Islands (GIs), Integrons, and Prophage regions have been explored in detail. RESULTS: The pan-genome ranges between a total of 5253-5857 genes with 2070 - 1899 core gene clusters. Some antimicrobial resistance genes have been identified in the core genome portion, but most of them were located in the dispensable genome. In addition, some well-known virulence factors described in pathogenic Corynebacterium species were located in the dispensable genome. A total of 115 phage species have been identified with only 44 intact prophage regions. CONCLUSION: This study presents a detailed comparative pangenome report of C. striatum. The species show a very slowly growing pangenome with relatively high number of genes in the core genome contributing to lower genomic variation. Prophage elements carrying AMR and virulence elements appear to be infrequent in the species. GIs appear to offer a prominent role in mobilizing antibiotic resistance genes in the species and integrons occur at a frequency of 50% in the species. Control strategies should be directed against virulence and resistance determinants carried on the core genome and those frequently occurring in the accessory genome.

Nanotechnology-Based Strategies to Combat Multidrug-Resistant Candida auris Infections.

An emerging multidrug-resistant pathogenic yeast called Candida auris has a high potential to spread quickly among hospitalized patients and immunodeficient patients causing nosocomial outbreaks. It has the potential to cause pandemic outbreaks in about 45 nations with high mortality rates. Additionally, the fungus has become resistant to decontamination techniques and can survive for weeks in a hospital environment. Nanoparticles might be a good substitute to treat illnesses brought on by this newly discovered pathogen. Nanoparticles have become a trend and hot topic in recent years to combat this fatal fungus. This review gives a general insight into the epidemiology of C. auris and infection. It discusses the current conventional therapy and mechanism of resistance development. Furthermore, it focuses on nanoparticles, their different types, and up-to-date trials to evaluate the promising efficacy of nanoparticles with respect to C. auris.

Binary CuO\CoO nanoparticles inhibit biofilm formation and reduce the expression of papC and fimH genes in multidrug-resistant Klebsiella oxytoca.

BACKGROUND AND AIM: Binary copper-cobalt oxide nanoparticles (CuO\CoO NPs) are modern kinds of antimicrobials, which may get a lot of interest in clinical application. This study aimed to detect the effect of the binary CuO\CoO NPs on the expression of papC and fimH genes in multidrug-resistant (MDR) isolates of Klebsiella oxytoca to reduce medication time and improve outcomes. METHODS: Ten isolates of K. oxytoca were collected and identified by different conventional tests besides PCR. Antibiotic sensitivity and biofilm-forming ability were carried out. The harboring of papC and fimH genes was also detected. The effect of binary CuO\CoO nanoparticles on the expression of papC and fimH genes was investigated. RESULTS: Bacterial resistance against cefotaxime and gentamicin was the highest (100%), while the lowest percentage of resistance was to amikacin (30%). Nine of the ten bacterial isolates had the ability to form a biofilm with different capacities. MIC for binary CuO\CoO NPs was 2.5 µg/mL. Gene expression of papC and fimH was 8.5- and 9-fold lower using the NPs. CONCLUSION: Binary CuO\CoO NPs have a potential therapeutic effect against infections triggered by MDR K. oxytoca strains due to the NPs-related downregulation ability on the virulence genes of K. oxytoca.

Anti-capsular activity of CuO nanoparticles against Acinetobacter baumannii produce efflux pump.

Copper oxide nanoparticles are modern kinds of antimicrobials, which may get a lot of interest in the clinical application. This study aimed to detect the anti-capsular activity of CuO nanoparticles against Acinetobacter baumannii produce efflux pump. Thirty-four different clinical A. baumannii isolates were collected and identified by the phenotypic and genetic methods by the recA gene as housekeeping. Antibiotic sensitivity and biofilm-forming ability, capsular formation were carried out. The effect of CuO nanoparticles on capsular isolates was detected, the synergistic effects of a combination CuO nanoparticles and gentamicin against A. baumannii were determined by micro broth checkerboard method, and the effect of CuO nanoparticles on the expression of ptk, espA and mexX genes was analyzed. Results demonstrated that CuO nanoparticles with gentamicin revealed a synergistic effect. Gene expression results show reducing the expression of these capsular genes by CuO nanoparticles is major conduct over reducing A. baumannii capsular action. Furthermore, results proved that there was a relationship between the capsule-forming ability and the absence of biofilm-forming ability. As bacterial isolates which were negative biofilm formation were positive in capsule formation and vice versa. In conclusion, CuO nanoparticles have the potential to be used as an anti-capsular agent against A. baumannii, and their combination with gentamicin can enhance their antimicrobial effect. The study also suggests that the absence of biofilm formation may be associated with the presence of capsule formation in A. baumannii. These findings provide a basis for further research on the use of CuO nanoparticles as a novel antimicrobial agent against A. baumannii and other bacterial pathogens, also to investigate the potential of CuO nanoparticles to inhibit the production of efflux pumps in A. baumannii, which are a major mechanism of antibiotic resistance.

T cell subsets, regulatory T, regulatory B cells and proinflammatory cytokine profile in Schistosoma haematobium associated bladder cancer: First report from Upper Egypt.

BACKGROUND: The function of different populations of the immune system in bladder cancer (BCa) is well established. However, the cohesive role of the immune cell profile of schistosomal BCa at systemic and tissue levels is still lacking, especially in endemic countries. The balance hypothesized between protumorigenic and antitumor molecules determines the prognosis of tumor progression. This study aimed to investigate the frequency of T cell subsets at both blood and tumor tissue, regulatory T(Treg), regulatory B cells (Breg) and proinflammatory cytokines in S. haematobium-related BCa patients in Egypt. METHODOLOGY/PRINCIPAL FINDINGS: The frequency of T cell subsets at both blood and tumor tissue, regulatory T(Treg), regulatory B cells (Breg) were studied by flow cytometry and proinflammatory cytokines by ELISA in S. haematobium-related BCa patients in Egypt. The results indicated a significant increase in the activity of T-cell populations, particularly CD3+, CD4+, and regulatory T cells (Tregs), and a decrease in cytotoxic CD8+ T cells in the patient group. An increased proportion of CD19+CD24+CD38+ Bregs and proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) was also observed. However, T-cell subpopulations in the tumor microenvironment showed a significant reduction in cancer patients compared to controls. Moreover, positive correlations were observed between the frequencies of Bregs and Tregs, suggesting the promotion of cancer progression besides their relation to the intensity of schistosomal infection. CONCLUSIONS/SIGNIFICANCE: Trapped Schistosoma haematobium eggs in bladder tissue might lead to persistent inflammation that contributes to immunomodulation and promotes tumor progression, as evidenced by the increase in peripheral T helper, Tregs, Bregs and serum tumor-promoting cytokines. Considering the role and integrated functions of specific immune responses in BCa could help future diagnostic and therapeutic implications.

Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives.

The wide spread of antibiotic resistance has been alarming in recent years and poses a serious global hazard to public health as it leads to millions of deaths all over the world. The wide spread of resistance and sharing resistance genes between different types of bacteria led to emergence of multidrug resistant (MDR) microorganisms. This problem is exacerbated when microorganisms create biofilms, which can boost bacterial resistance by up to 1000-fold and increase the emergence of MDR infections. The absence of novel and potent antimicrobial compounds is linked to the rise of multidrug resistance. This has sparked international efforts to develop new and improved antimicrobial agents as well as innovative and efficient techniques for antibiotic administration and targeting. There is an evolution in nanotechnology in recent years in treatment and prevention of the biofilm formation and MDR infection. The development of nanomaterial-based therapeutics, which could overcome current pathways linked to acquired drug resistance, is a hopeful strategy for treating difficult-to-treat bacterial infections. Additionally, nanoparticles' distinct size and physical characteristics enable them to target biofilms and treat resistant pathogens. This review highlights the current advances in nanotechnology to combat MDR and biofilm infection. In addition, it provides insight on development and mechanisms of antibiotic resistance, spread of MDR and XDR infection, and development of nanoparticles and mechanisms of their antibacterial activity. Moreover, this review considers the difference between free antibiotics and nanoantibiotics, and the synergistic effect of nanoantibiotics to combat planktonic bacteria, intracellular bacteria and biofilm. Finally, we will discuss the strength and limitations of the application of nanotechnology against bacterial infection and future perspectives.

oprL Gene Sequencing, Resistance Patterns, Virulence Genes, Quorum Sensing and Antibiotic Resistance Genes of XDR Pseudomonas aeruginosa Isolated from Broiler Chickens.

Background: Pseudomonas aeruginosa is incriminated in septicemia, significant economic losses in the poultry production sector, and severe respiratory infections in humans. This study aimed to investigate the occurrence, oprL sequencing, antimicrobial resistance patterns, virulence-determinant, Quorum sensing, and antibiotic resistance genes of P. aeruginosa retrieved from broiler chickens. Methods: Two hundred samples were collected from 120 broiler chickens from broiler farms at Ismailia Governorate, Egypt. Consequently, the bacteriological examination was conducted and the obtained P. aeruginosa strains were tested for oprL gene sequencing, antibiogram, and PCR screening of virulence, Quorum sensing, and antibiotic resistance genes. Results: The overall prevalence of P. aeruginosa in the examined birds was 28.3%. The oprL gene sequence analysis underlined that the tested strain expressed a notable genetic identity with various P. aeruginosa strains isolated from different geographical areas in the USA, India, China, Chile, and Ghana. PCR evidenced that the obtained P. aeruginosa strains, carrying virulence-related genes: oprL, toxA, aprA, phzM, and exoS in a prevalence of 100%, 100%, 42.5%, 33.3%, and 25.9%, respectively. Moreover, the recovered P. aeruginosa strains possessed the Quorum sensing genes: lasI, lasR, rhlI, and rhlR in a prevalence of 85.2%, 85.2%, 81.5%, and 81.5%, respectively. Furthermore, 40.7% of the isolated P. aeruginosa were XDR to seven antimicrobial classes, possessing sul1, bla TEM, tetA, bla CTX-M, bla OXA-1, and aadA1 genes. Conclusion: As we can tell, this is the first report emphasizing the evolution of XDR P. aeruginosa strains from broiler chicken in Egypt, which is supposed to be a serious threat to public health. The emerging XDR P. aeruginosa in poultry frequently harbored the oprL, toxA, and aprA virulence genes, the lasI, lasR, rhlI, and rhlR Quorum sensing genes, and the sul1, bla TEM, tetA, bla CTXM, bla OXA-1, and aadA1 resistance genes.

Isolation and Molecular Characterization of Corynebacterium pseudotuberculosis: Association with Proinflammatory Cytokines in Caseous Lymphadenitis Pyogranulomas.

Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a causative agent of numerous chronic diseases, including caseous lymphadenitis (CLA) in sheep and goats, which has a zoonotic potential in humans in addition to a poor therapeutic response. In this study, out of 120 collected samples, only 12 (10%) were positive for C. pseudotuberculosis by PCR and by intraperitoneal injection of male Guinea pigs and then characterized for antimicrobial susceptibility and its genetic-relatedness by enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), which showed 2-4 bands ranging from 100 to 3000 bp that can be clustered into four clusters (C1-C4). Despite the serotype biovar 1 only infecting sheep and goats, ERIC-PCR reveals intra-subtyping variation. Examination of affected LNs and organs revealed marked enlargement with either thick creamy green pus or multiple abscesses of variable sizes with a central caseated core surrounded by dense fibrous capsule. A histopathological examination revealed a central necrotic core surrounded by a peripheral mantle of mononuclear cells and a fibrous capsule. Positive immune expression of nuclear factor kappa B (NF-κB/p65) and interleukin-1ß (IL-1ß) and negative expression of tumor necrosis factor (TNF) in CLA is the first report to our knowledge. Conclusion: In CLA pyogranulomas, IL1ß is a more crucial proinflammatory cytokine than TNF in the regulation of C. pseudotuberculosis infection, which is accompanied by marked NF-κB immunoexpression. Therefore, the NF-κB/p65 signaling pathway is involved in the activation of IL1ß, and additional immunohistochemical studies are required to determine the various roles of NF-κB/p65 in the inflammatory response within CLA pyogranulomas to control this pathogen.

Heparanase is the possible link between monkeypox and Covid-19: robust candidature in the mystic and present perspective.

Heparanase (HPSE) is an endoglycosidase cleaves heparan sulfate (HS) and this contributes to the degradation and remodeling of the extracellular matrix. HS cleaved by HPSE induces activation of autophagy and formation of autophagosommes which facilitate binding of HPSE to the HS and subsequent release of growth factors. The interaction between HPSE and HS triggers releases of chemokines and cytokines which affect inflammatory response and cell signaling pathways with development of hyperinflammation, cytokine storm (CS) and coagulopathy. HPSE expression is induced by both SARS-CoV-2 and monkeypox virus (MPXV) leading to induction release of pro-inflammatory cytokines, endothelial dysfunction and thrombotic events. Co-infection of MPX with SARS-CoV-2 may occur as we facing many outbreaks of MPX cases during Covid-19 pandemic. Therefore, targeting of HPSE by specific inhibitors may reduce the risk of complications in both SARS-CoV-2 and MPXV infections. Taken together, HPSE could be a potential link between MPX with SARS-CoV-2 in Covid-19 era.