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Novel natural and synthetic anticandidal therapeutic peptides to combat drug resistant infections

Candida species are considered as common flora of the healthy human mycobiome and occur on skin, mucosal surfaces of gastrointestinal and genitourinary tracks. Pathogenic Candida spp., reported to cause skin, vaginal and oral infections as well as systemic infection in immunocompromised humans. Extensive use of antifungal agents has increased the drug resistance among pathogenic strains of Candida. The biofilm formation ability of Candida strains also adds on resistance to antifungal drugs. This increased resistant desperately requires alternative antifungal agents to overcome this problem. To this effect, recently naturally occurring AMPs and synthetically modified peptides, are effectively being used as promising antifungal agents.

Short peptides display better permeability to cross the yeast membrane, thus short antifungal peptide were designed using sequences from APD database. Antifungal potential of designed peptides was predicted in terms of protein binding potential, amphipathicity, hydrophobicity, hydrophilicity and net charge. In vitro synthetic peptides (SK08 and pep2) showed anticandidal activity against various test strains. Natural peptides are potent antifungal agents, considering these facts, we focused on screening potent antifungal peptides from Bacillus sp. strain A52 and Bacillus sp. strain SVDS-15 that were found to inhibit various pathogenic Candida strains. However, both of these lipopeptides exhibited hemolytic activity. Interestingly, the lipopeptides did not show any phytotoxic effect in seed germination experiments. Further, emulgel formulations were developed containing cetomacrogol 1000 and lipopeptides (A52 and SVDS-15) which showed in vitro, antimicrobial activity. No irritation effects were observed with formulation during animal studies using BALB/c mice indicating their potential for external therapeutic applications.

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A rising threat of the rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram-negative pathogens is a matter of public health concern worldwide. The current study was undertaken to investigate the prevalence of Metallo-beta-lactamase producing gram-negative bacteria isolated from chicken meat in Bharatpur. The study was conducted for the period of 3 months from April 2023 to June 2023 in the Microbiology laboratory of Balkumari College, Bharatpur, Chitwan. Among the 40 collected sample, 12 (30%) isolates were E. coli, 10(25%) Citrobacter ,8(20%) Salmonella spp., 4(10%) Proteus spp., 4(10%) Shigella spp. and 2(5%) Klebsiella spp. Out of 12 isolates of E. coli species 10 (83.34%) isolates were found Multidrug resistance and 8 isolates were MBL positive. Out of 10 isolates of Citrobacter species, 7(70%) were found Multidrug resistance and 9 isolates were MBL positive. Similarly, out of 8 isolates of Salmonella species, 6(75%) were found to be Multidrug resistance and 5 isolates were MBL positive. Among the 4 isolates of Proteus species, 2(50%) were found to be Multidrug resistance and 3 were MBL positive. Out of 4 isolates of Shigella species, 3(75%) isolates were found to be Multidrug resistance and 3 isolates were MBL positive. Likewise, out of 2 isolates of Klebsiella species, 1 was found to be Multidrug resistance and both isolates were MBL positive.

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Optimization of Polyvinyl Alcohol and Gum Tragacanth Membrane with Ciprofloxacin-loaded Gold Nanoparticles for Wound Healing Applications

Bandages, Gauzes and Alcoholic pads have widely been used for wound healing. However due to few limitations hydrophilic membranes loaded with nanoparticles have been explored rarely as a wound healing material. This study aimed to synthesize and characterize Polyvinyl Alcohol (PVA) and Gum Tragacanth(GT) membrane having different concentrations of gold nanoparticles(AuNPs) loaded with Ciprofloxacin as bacterial infection is one of the major problem for wound healing. Gold and CIP-loaded nanoparticles were successfully prepared by Turkevich method and confirmed by Fourier-transform infrared spectroscopy. To analyze the hydrophilicity of membrane swelling test as well as contact angle analysis were performed. In summary, this study demonstrated that hydrophilic membrane of PVA/GUM T. having 500ul concentration of CIP-loaded AuNPs can be used as wound healing materials without affecting their biocompatibility.

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Highest priority critically important antimicrobial-resistant Escherichia coli and Salmonella spp. isolated from pork and chicken meat from Argentina
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Between June and September 2023, a total of 80 meat samples (48 and 32 from pork and
chicken, respectively) were collected from 16 retail markets in La Plata, Argentina.
Antimicrobial susceptibility was evaluated by agar diffusion, and PCR was used to identify
resistance genes. All markets were positive for at least one resistant E. coli. Eighty-four
resistant E. coli and two Salmonella spp. were isolated. Resistance to ciprofloxacin was
observed in 65 E. coli, 25 from pork, and 40 from chicken meat. Resistance to cefotaxime
was observed in 49 E. coli isolates, 14 from pork, and 35 from chicken meat. Seventy-five E.
coli isolates were multidrug resistant; twenty-four isolates showed resistance to four
antibiotic classes; and 20 strains were resistant to five antibiotic classes. Resistance was
most common to ampicillin (91.7%), tetracycline (78.6%), ciprofloxacin (77.4%), cefotaxime
(58.3%), chloramphenicol (48.8%), amoxicillin/clavulanic acid (47.6%), sulfamethoxazole-
trimethoprim (45.2%), fosfomycin (32.1%), gentamicin (22.6%), ceftazidime (8.3%), and
cefoxitin (4.8%). Fourteen E. coli isolated from chicken meat showed resistance to three of
the HPCIA cefotaxime/cefepime, ciprofloxacin, and fosfomycin. Resistance to 3rd and 4th
generation cephalosporin was associated with bla CTX-M genes; 12 E. coli were isolated from
pork and 33 from chicken meat. bla CTX-M alleles were grouped by specific PCR as follows: 1
bla CTX-M-1/15 ; 17 bla CTX-M-2 ; 5 bla CTX-M-9/14 ; and 5 bla CTX-M-8/25 . The results prove that the presence of resistant E. coli in pork and chicken meat can be a source of multiple resistance genes.

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"Antibiotics in a Changing World: Resistance, Ecology, and Public Health Conundrums"
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The world of antibiotics is undergoing a significant transformation, driven by the dual challenges of antimicrobial resistance and ecological ramifications associated with their use. This thesis provides a comprehensive examination of the intricate relationship between antibiotics, public health, and the environment, shedding light on the multifaceted problems that this interplay creates.

The research scrutinizes the global crisis of antibiotic resistance, investigating its origins, underlying mechanisms, and its alarming proliferation. Antibiotic-resistant bacteria pose a serious threat to the effectiveness of these crucial drugs in the fight against infectious diseases. This necessitates a reevaluation of antibiotic use and the development of innovative strategies to curb resistance also focusing on the ecological consequences of antibiotic utilization. While antibiotics are designed to target specific pathogens, their impact extends to the broader microbial communities they encounter. The research delves into the effects of antibiotics on ecosystem balance, with a particular emphasis on their contribution to the growing problem of environmental antibiotic resistance.

This thesis offers a holistic perspective on the evolving landscape of antibiotics through a comprehensive analysis of these interconnected aspects. It emphasizes the urgent need for a global response to address resistance, advocates for a balanced approach to antibiotic usage, and underscores the pivotal role of public health strategies in managing these intricate challenges

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Approaches to reduce the side effects of antibiotic therapy in premature newborns
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Significant risk of drug therapy side effects in newborns, especially in premature neonates, is associated with the immaturity of a number of enzyme systems and biotransformation mechanisms and pharmacokinetics specificity. First of all, it is associated with the immaturity of the microsomal mechanism of hepatic cells. Newborns have lower concentrations of cytochrome P450, NADPH-oxidase, cytochrome-C reductase, (uridine diphosphate)-glucuronyl transferase, as well as enzymatic and non-enzymatic modulators of the thiol-disulfide system. Low activity of the antioxidant system and endogenous antioxidants enhances the ROS formation during biotransformation of antibiotics and increase their toxicity at concentrations safe for adults, resulting in increased hepatotoxicity. In Zaporizhzhya region (Ukraine), in chronic pulmonary suppuration, transaminase levels increased in 17% of children treated with chloramphenicol and aminoglycosides, in 7.8% with semi-synthetic penicillins and in 5.3% with cephalosporins and macrolides, as well as in 34.5% of children receiving combined therapy. This makes it necessary to reduce dosages, usually by infrequent administration of drugs, and to conduct laboratory monitoring not only of the hepatobiliary system, but also of the antioxidant glutathione system. Another important approach for premature infants in the first weeks of life to reduce antibiotic therapy side effects, including hepatotoxicity, is the administration of agents modulating the activity of the glutathione system. The difficulty in implementing this approach is the strict requirements for safety and proven efficiency for drugs in neonatal intensive care. We consider the use of thioazatate (thiotriazolin), a drug licensed in Ukraine with proven hepatoprotective and cardioprotective activity and a high safety profile.

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Revitalizing Antibiotics: Strategies to Combat Resistance and Restore Effectiveness
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The rising issue of antibiotic resistance has emerged as a serious global health problem, compromising our capacity to successfully tackle bacterial diseases. Antibiotic abuse and misuse have hastened the development of resistance, leaving many once-effective medications useless. This research investigates ways for reversing antibiotic resistance, with a special emphasis on rejuvenating older drugs.

Several main techniques are being investigated in the attempt to "Make Old Antibiotics Great Again." First, we investigate the mechanisms behind antibiotic resistance, offering information on the evolutionary processes that drive bacterial adaptability. Following that, we will look at the possibilities of antibiotic combination treatment, a strategy that can improve the efficacy of older antibiotics by utilising synergistic drug interactions.

Furthermore, we investigate the potential of antibiotic stewardship programmes, stressing the ethical use of antibiotics to lessen selection pressure for resistant bacteria. Rapid molecular testing, for example, is highlighted as a vital tool for accurate antibiotic selection, improving treatment regimens, and limiting resistance development.

The importance of research and development activities in the quest to discover new antibiotics is underlined, as it provides a long-term solution to the resistance challenge. Furthermore, we discuss the importance of policy interventions and global cooperation in creating the landscape of antibiotic resistance, eventually recommending a united response to this critical issue.

In summary, this study underlines the need to reverse antibiotic resistance, emphasises the potential of older antibiotics when used wisely, and recommends a holistic strategy incorporating scientific, medical, and policy strategies to address this emerging danger to public health.

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Asking Bing with GPT-4 about antibiotical uses of clays

In this work Microsoft Bing chat with GPT-4, which will be henceforth referred to simply as Bing, was used for researching the antibiotical use of clays, by submitting three requests that were literally:

+) Write a bullet list of the most important points concerning research on the use of clay minerals for preparing antibiotics;

+) Write a bullet list of suggestions for future and original research, not done before, on the use of clay minerals for preparing antibiotics;

+) Write a bullet list of the most important results of clinical trials of clay minerals as antibiotics.

Bing's answers were extensive, containing information on mineralogical and health issues.

Bing's also suggested follow up questions, some of which will be also included, and that expanded the topics considered to domains of ethics and arguably even politics, with repeated re references to "respecting the traditional knowledge and practices of indigenous or local communities that have used clay minerals for medicinal purposes for centuries", including the answer to the question, suggested by Bing, "How can we improve the antibiotic activity and specificity of clay minerals?".

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Resistotyping of Salmonella spp. and Staphylococcus aureus from milk and milk products sold in Sabon-gari and Zaria Local Government Areas of Kaduna State, Nigeria.
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This study investigated the resistotyping of Salmonella spp. and Staphylococcus aureus from milk and milk products sold in Sabon-gari and Zaria Local Government Areas of Kaduna State, Nigeria. A total of 122 isolates Salmonella spp. (65) and Staphylococcus aureus (57) were isolated from 400 milk and milk products. The isolates were subjected to antimicrobial Susceptibility Testing using the disc diffusion and E-test methods. The results obtained from the study indicated that 39 (31.967%) isolates were sensitive to all tested antibiotics, while 47 (38.525%) were resistant to a single antibiotic. 36 (29.508%) were resistant to two antibiotics, and none showed resistance to at least three antibiotics. None showed resistance to all four antibiotics. Resistance rate were most frequently observed in Tetracycline at 80 (65.574%), followed by Ampicillin at 39 (31.967%), Gentamicin, and Ciprofloxacin both at 00 (00.000%). After comparing with the CLSI and EUCAST breakpoints, the resistance rate with CLSI was Tetracycline at 104 (85.245%), followed by Ampicillin at 39 (66.393%), Ciprofloxacin at 14 (11.475%), and Gentamicin at 06 (04.918%). The resistance rate with EUCAST was Tetracycline at 122 (100.000%), followed by Ampicillin at 110 (90.164%), Ciprofloxacin at 88 (72.131%), and Gentamicin at 17 (13.934%). Based on these findings, it has shown that Salmonella spp. and Staphylococcus aureus found in milk and milk products within Sabon-gari and Zaria Local Government Areas have a high resistance to the antibiotics tested. It is imperative that urgent actions are taken to address the growing menace of AMR and prevent the spread of antibiotic-resistant pathogens.

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Isolation and Identification of Antimicrobial Multidrug Resistant Bacteria From Street Food

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One of the unpleasant problems and one that could have significant effects in the near future is the sharp rise in zoonotic multi-drug resistant (MDR) bacteria (Staphylococcus aureus, Streptococcus, Salmonella spp.). The enlarging and indiscriminate use of antimicrobials in the production of food, fish, and crops has led to a severe problem with multidrug resistance in human as well as animal health, particularly in school-age children. Therefore, it is crucial to learn whether Bangladeshi street food contains Salmonella and MDR Staphylococcus. Staphylococcus, Streptococcus, and Salmonella prevalence in street food variants and the pattern of antimicrobial resistance of isolated multidrug resistant bacteria were investigated in a cross-sectional study. The study was conducted at five street food carts near schools in Gopalganj Sadar, Bangladesh. MIU TEST, Oxidase, and Citrate tests) are carried out precisely in order to isolate and identify bacteria that are multidrug resistant. Twenty commercially available antimicrobials that are frequently employed in veterinary as well medical settings in Bangladesh were tested for antibiotic susceptibility using the disc diffusion method. Each of the food samples examined for the research included MDR Salmonella (resistant to up to six of the eight tested antimicrobials). Ampicillin and Amoxicillin had the greatest resistance rates (100%) while Doxycycline had the lowest rates (approximately 15%) among the identified Bacteria. Additionally, numerous street food products have different levels of Salmonella's antibiotic resistance.