Drug-resistant Microorganisms Research Articles

Engineering of chimeric enzymes with expanded tolerance to ionic strength.

Antimicrobial resistance poses a significant global threat, reaching dangerously high levels as reported by the World Health Organization. The emergence and rapid spread of new resistance mechanisms, coupled with the absence of effective treatments in recent decades, have led to thousands of deaths annually from infections caused by drug-resistant microorganisms. Consequently, there is an urgent need for the development of new compounds capable of combating antibiotic-resistant bacteria. A promising class of molecules exhibiting potent bactericidal effects is peptidoglycan hydrolases. Previously, we cloned and characterized the biochemical properties of the M23 catalytic domain of the EnpA (EnpACD) protein from Enterococcus faecalis. Unlike other enzymes within the M23 family, EnpACD demonstrates broad specificity. However, its activity is constrained under low ionic strength conditions. In this study, we present the engineering of three chimeric enzymes comprising EnpACD fused with three distinct SH3b cell wall-binding domains. These chimeras exhibit enhanced tolerance to environmental conditions and sustained activity in bovine and human serum. Furthermore, our findings demonstrate that the addition of SH3b domains influences the activity of the chimeric enzymes, thereby expanding their potential applications in combating antimicrobial resistance.IMPORTANCEThese studies demonstrate that the addition of the SH3b-binding domain to the EnpACD results in generation of chimeras with a broader tolerance to ionic strength and pH values, enabling them to remain active over a wider range of conditions. Such approach offers a relatively straightforward method for obtaining antibacterial enzymes with tailored properties and emphasizes the potential for proteins' engineering with enhanced functionality, contributing to the ongoing efforts to address antimicrobial resistance effectively.

New Schiff Base Derived Organotin (IV) Complexes: Synthesis, Characterization, In vitro and In silico Biological Studies

Aims: The creation and testing of new Schiff base-based antibacterial organotin (IV) complexes were the objectives of this investigation. background: Due to developed resistance, antibiotics that were once often used to treat microorganisms are no longer effective against them. It is thought that organotin compounds synthesized from Schiff bases have significant pharmacological effectiveness and work well as antibacterial agents Background: Due to developed resistance, antibiotics that were once often used to treat microor-ganisms are no longer effective against them. It is thought that organotin compounds synthesized from Schiff bases have significant pharmacological effectiveness and work well as antibacterial agents. Methods: Thiocarbohydrazide and dehydroacetic acid were condensed to create the Schiff base, followed by processing with dialkyltin(IV)dichloride to synthesize the final product. Modern an-alytical techniques were used to clarify the compounds' probable structural details. The crystalline nature of the produced compounds was tested using PXRD. Results: All of the compounds were thermally stable up to 300°C. All of the synthesized com-plexes showed potent antibacterial activity in the range of 250 to 400 μg/ml. Furthermore, the computational biology research showed that, in contrast to ligands, which had a binding energy of -7.3 to -7.4 kcal/mol, complexes interacted well with dihydropteroate synthase and DNA gy-rase. Conclusion: The current study offered a unique technique for synthesizing diorganotin(IV) de-rivatives of N-substituted Schiff bases that are physiologically active. The results show that the chemicals created are promising antibacterial mediators against diseases that affect humans in the modern world. It might also open the door to future studies on drug-resistant microorganisms that could have biological uses.

Providing insight into the mechanism of action of cationic lipidated oligomers using metabolomics.

The increasing resistance of clinically relevant microbes against current commercially available antimicrobials underpins the urgent need for alternative and novel treatment strategies. Cationic lipidated oligomers (CLOs) are innovative alternatives to antimicrobial peptides and have reported antimicrobial potential. An understanding of their antimicrobial mechanism of action is required to rationally design future treatment strategies for CLOs, either in monotherapy or synergistic combinations. In the present study, metabolomics was used to investigate the potential metabolic pathways involved in the mechanisms of antibacterial activity of one CLO, C12-o-(BG-D)-10, which we have previously shown to be effective against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. The metabolomes of MRSA ATCC 43300 at 1, 3, and 6 h following treatment with C12-o-(BG-D)-10 (48 µg/mL, i.e., 3× MIC) were compared to those of the untreated controls. Our findings reveal that the studied CLO, C12-o-(BG-D)-10, disorganized the bacterial membrane as the first step toward its antimicrobial effect, as evidenced by marked perturbations in the bacterial membrane lipids and peptidoglycan biosynthesis observed at early time points, i.e., 1 and 3 h. Central carbon metabolism and the biosynthesis of DNA, RNA, and arginine were also vigorously perturbed, mainly at early time points. Moreover, bacterial cells were under osmotic and oxidative stress across all time points, as evident by perturbations of trehalose biosynthesis and pentose phosphate shunt. Overall, this metabolomics study has, for the first time, revealed that the antimicrobial action of C12-o-(BG-D)-10 may potentially stem from the dysregulation of multiple metabolic pathways.IMPORTANCEAntimicrobial resistance poses a significant challenge to healthcare systems worldwide. Novel anti-infective therapeutics are urgently needed to combat drug-resistant microorganisms. Cationic lipidated oligomers (CLOs) show promise as new antibacterial agents against Gram-positive pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Understanding their molecular mechanism(s) of antimicrobial action may help design synergistic CLO treatments along with monotherapy. Here, we describe the first metabolomics study to investigate the killing mechanism(s) of CLOs against MRSA. The results of our study indicate that the CLO, C12-o-(BG-D)-10, had a notable impact on the biosynthesis and organization of the bacterial cell envelope. C12-o-(BG-D)-10 also inhibits arginine, histidine, central carbon metabolism, and trehalose production, adding to its antibacterial characteristics. This work illuminates the unique mechanism of action of C12-o-(BG-D)-10 and opens an avenue to design innovative antibacterial oligomers/polymers for future clinical applications.

Synthesis of citral-tryptamine fused selenium nanospheres (CT@SeNP's) and exploration of their anticancer, antibacterial, and electrochemical sensor applications

A broad spectrum of antibiotics with multiple mechanisms of action is urgently required to combat the growing public health threat posed by drug-resistant pathogenic microorganisms. Biomedical researchers have concentrated on creating novel antibacterial and anticancer therapies due to the limited availability of conventional antibacterial and anticancer medications. In this study citral-tryptamine molecule was synthesized and characterized using 1HNMR , 13CNMR , LCMS and FT-IR spectral techniques and various biological properties of synthesized molecules were investigated using several in silico approaches such as molecular docking, ADME, PASS analysis and bioactive score. Using citral-tryptamine molecule, selenium nanoparticles (CT@SeNP's) were synthesized and characterized using different spectral and imaging techniques such as UV–Visible spectra, SEM, FTIR, EDX, XRD and DLS. EDX and mapping were used to investigate the relevant atoms and their distribution. Three significant signals from the EDX corresponding to C atom (15.4 %), along with signals from the Se atom (80.9 %) and the N atom (3.7 %). CT@SeNP's showed excellent antibacterial property against MRSA. The minimum inhibitory concentration of CT@SeNP's was found to be 20±0.36 mm with a good zone of inhibition in a dose dependent manner. CT@SeNP's was treated with both normal and cervical cancer cell lines such as SiHa to investigate the dose optimization and cytotoxicity by MTT assay. The nanoparticle showed an IC50 value is 0.68 µM and the data strongly suggested that CT@SeNP's could have a high potential in future medication development against MRSA and cervical cancer cells. The proper development and manufacturing of electrocatalytic nanomaterials are essential for enhancing the performance of non-enzymatic electrochemical sensors. The electrochemical sensing of H2O2 was enhanced by nanocomposite CT@SeNPs, which have a low detection limit of 60.96 nM and can detect H2O2 in a wide range of concentrations, from 25 µM to 250 µM. Thus, an efficient sensing platform for non-enzymatic H2O2 detection was discovered by this investigation.

Anthrapyrazolone functionalized Oligo(ethylene glycol)methyl ether methacrylates based fluorescent polymeric hydrogel for selective detection of Tetracycline drug

Tetracycline (TC) antibiotics are essential for treating bacterial infections; however, overuse and improper disposal place the environment in danger and promote the growth of drug-resistant microorganisms. Monitoring their impact on living organisms is vital. Polymeric-based hydrogels offer promise in antibiotic detection due to their versatility and biocompatibility, despite their uncommon use for this purpose. In this study, we have synthesized a fluorescent polymeric hydrogel, P(OEGMA-co-DIMA) utilizing oligo(ethylene glycol)methyl ether methacrylates (OEGMA) and laboratory-synthesized fluorescent anthrapyrazolone containing monomer, 2-(benzo[1,2,3-cd:4,5,6-c’d]bis(indazole)-2(7H)-yl)ethyl methacrylate (DIMA) for the fluorometric detection of TC in the aqueous medium. The P(OEGMA-co-DIMA) hydrogel exhibited exceptional affinity towards TC while exhibiting high selectivity. The chemosensing behavior of the hydrogel was also compared with the DIMA monomer. Upon adding TC, emission analysis revealed a notable quenching in the emission intensity of the P(OEGMA-co-DIMA) hydrogel as well as the DIMA monomer. The Stern Volmer rate constants (Ksv) of the hydrogel (Ksv = 9.99 x 103 M−1) in water and DIMA (Ksv = 25.63 x 103 M−1) in acetonitrile showed a higher quenching rate constant with a limit of detections (LODs) of 1.3 nM and 0.11 nM. Turn-off fluorescence behavior occurs via a static quenching mechanism through a photoinduced electron transfer process and intermolecular hydrogen bonding. To validate the selectivity, the interference analyses in an aqueous medium with different antibiotics are provided. To rationalize the real-time applicability of the hydrogel, studies were extended to water samples obtained from deionized water, tap water, lake water, and also in milk samples. The recovery rate and LOD for real samples ranged from 83.8 % to 111 % and 0.83 to 3.6 nM, respectively.

Elongation Factor P is Required for Processes Associated with Acinetobacter Pathogenesis

Antibiotic resistance is one of the world’s fastest-growing and most prevalent problems today. The influx of antibiotics within our environment from inadequate antibiotic stewardship has led to a surge of drug-resistant microorganisms. The CDC has classified Carbapenem-resistant Acinetobacter (CRA) as an urgent threat within this crisis. New drug development is imperative to combat infections caused by drug-resistant pathogens such as CRA. Bacterial translation, the process of protein synthesis by the ribosome, is a common target for new antibiotic development. Elongation factor P (EF-P) is a universally conserved translation factor required for antibiotic resistance in many bacteria. In this study, we assessed the importance of EF-P in processes associated with Acinetobacter pathogenesis. In the absence of EF-P, Acinetobacter baylyi displays decreased biofilm formation, surface-associated motility, and resistance to beta-lactams and carbapenems. This data holds hope for future drug development targeting EF-P in pathogens closely related to A. baylyi. KEYWORDS: Acinetobacter baylyi; Translation; Ribosome; Elongation Factor P; Polyproline; Biofilm; Surface Associated Motility; Antibiotic Resistance

Reviewing the Therapeutic Potential of Plant-based Natural Products Against Multidrug-resistant Bacteria (MDR)

Abstract: The global health of individuals is severely threatened by drug-resistant microorganisms. Existing antibiotics available in the market, such as penicillin, cephalosporins, new β- lactams, aminoglycosides, macrolides, lincomycin, and quinolones, are losing their effectiveness due to overuse and inappropriate prescribing, among other factors. This situation underscores the urgent need to develop new antimicrobial agents. In response to this challenge, attention has been directed towards natural products derived from plants, which have been utilized for their medicinal benefits over an extended period. Various studies have demonstrated that plant-based natural products exhibit antibacterial action against multidrug-resistant (MDR) bacteria, making them potential candidates for the development of novel antimicrobial medicines. Plants belonging to classes, such as alkaloids, organosulfur compounds, terpenoids, coumarin, and polyphenols have been found to possess antimicrobial properties. This paper reviews the antimicrobial activity of plant-based natural products, whether used alone or in combination with conventional antibiotics. Additionally, the paper explores their mechanisms against drugresistant bacteria, the potential development of resistance against them, their current role in medicine, and their future perspectives.

Effect of Matricaria aurea Essential Oils on Biofilm Development, Virulence Factors and Quorum Sensing-Dependent Genes of Pseudomonas aeruginosa.

The emergence of drug-resistant microorganisms presents a substantial global public health threat. The increase in pathogens resistant to commonly prescribed antibiotics underscores the urgent requirement to explore alternative treatment strategies. This study adopts a novel approach by harnessing natural resources, specifically essential oils (EO), to combat bacterial pathogenicity. The primary aim of this research was to analyze the chemical composition of the aerial part of the Matricaria aurea (M. aureas) EO and evaluate its potential for inhibiting quorum sensing (QS) and disrupting biofilm formation in Pseudomonas aeruginosa (P. aeruginosa). The gas chromatography-mass spectrometry (GCMS) analysis unveiled that α-bisabolol oxide A constituted the predominant portion, comprising 64.8% of the total, with β-bisabolene at 6.3% and α-farnesene at 4.8% following closely behind. The antibiofilm efficacy was observed at concentrations of 0.3, 0.15, and 0.08 mg/mL, demonstrating negligible effects on cell viability. Furthermore, the EO from M. aurea effectively inhibited the formation of P. aeruginosa biofilms by diminishing aggregation, hydrophobicity, and swarming motility. Significantly, the EO treatment resulted in a conspicuous decrease in the production of pyocyanin, rhamnolipid, and extracellular polymeric substances (EPS), along with a reduction in the enzymatic activity of protease and chitinase. The EO effectively hindered QS by disrupting QS mechanisms, resulting in a marked decline in the secretion of N-Acyl homoserine lactone (AHL) molecules and the expression of phazA1 and aprA genes. This investigation offers compelling evidence supporting the potential of M. aurea EO as a promising therapeutic candidate for addressing infectious diseases induced by biofilm formation.

From "resistance genes expression" to "horizontal migration" as well as over secretion of Extracellular Polymeric Substances: Sludge microorganism’s response to the increasing of long-term disinfectant stress

Glutaraldehyde-Didecyldimethylammonium bromides (GDs) has been frequently and widely employed in livestock and poultry breeding farms to avoid epidemics such as African swine fever, but its long-term effect on the active sludge microorganisms of the receiving wastewater treatment plant was keep unclear. Four simulation systems were built here to explore the performance of aerobic activated sludge with the long-term exposure of GDs and its mechanism by analyzing water qualities, resistance genes, extracellular polymeric substances and microbial community structure. The results showed that the removal rates of CODCr and ammonia nitrogen decreased with the exposure concentration of GDs increasing. It is worth noting that long-term exposure to GDs can induce the horizontal transfer and coordinated expression of a large number of resistance genes, such as qacE, sul1, tetx, and int1, in drug-resistant microorganisms. Additionally, it promotes the secretion of more extracellular proteins, including arginine, forming a "barrier-like" protection. Therefore, long-term exposure to disinfectants can alter the treatment capacity of activated sludge receiving systems, and the abundance of resistance genes generated through horizontal transfer and coordinated expression by drug-resistant microorganisms does pose a significant threat to ecosystems and health. It is recommended to develop effective pretreatment methods to eliminate disinfectants.

Novel aminothiazoximone-corbelled ethoxycarbonylpyrimidones with antibiofilm activity to conquer Gram-negative bacteria through potential multitargeting effects

The emergence of drug-resistant microorganisms threatens human health, and it is usually exacerbated by the formation of biofilm, which forces the development of new antibacterial agents with antibiofilm activity. In this work, a novel category of aminothiazoximone-corbelled ethoxycarbonylpyrimidones (ACEs) was designed and synthesized, and some of the prepared ACEs showed potent bioactivity against the tested bacteria. In particular, imidazolyl ACE 6c showed better inhibitory activity towards Acinetobacter baumannii and Escherichia coli with MIC values both of 0.0066 mmol/L than norfloxacin. It was also revealed that imidazolyl ACE 6c not only possessed inconspicuous hemolytic rate and cytotoxicity, low drug resistance and no risk of penetrating the blood-brain barrier, but also exhibited obvious biofilm inhibition and eradication activities. The preliminary mechanism research suggested that imidazolyl ACE 6c could induce metabolic dysfunction by deactivating lactate dehydrogenase and promote the accumulation of reactive oxygen species to decrease the reduced glutathione and ultimately cause oxidative damage in bacteria. Furthermore, ACE 6c was also found that could insert into DNA to form the supramolecular complex of 6c-DNA and trigger cell death. The multidimensional effect might promote bacterial cell rupture, leading to the leakage of intracellular content. These findings manifested that novel imidazolyl ACE 6c as a potential multitargeting antibacterial agent with potent antibiofilm activity could provide new possibility for the treatment of refractory biofilm-intensified bacterial infections.

Hazards Associated with the Combined Application of Fungicides and Poultry Litter in Agricultural Areas.

In recent decades, the poultry farming industry has assumed a pivotal role in meeting the global demand for affordable animal proteins. While poultry farming makes a substantial contribution to food security and nutrition, it also presents environmental and public health challenges. The use of poultry litter as fertilizer for agricultural soils raises concerns about the transfer of pathogens and drug-resistant microorganisms from poultry farms to crop production areas. On the other hand, according to the Food and Agriculture Organization of the United Nations (FAO), fungicides represent the second most used chemical group in agricultural practices. In this context, agricultural soils receive the application of both poultry litter as a fertilizer and fungicides used in agricultural production. This practice can result in fungal contamination of the soil and the development of antifungal resistance. This article explores the necessity of monitoring antifungal resistance, particularly in food production areas with co-application of poultry litter and fungicides. It also highlights the role of fungi in ecosystems, decomposition, and mutualistic plant associations. We call for interdisciplinary research to comprehensively understand fungal resistance to fungicides in the environment. This approach seeks to promote sustainability in the realms of human health, agriculture, and the environment, aligning seamlessly with the One Health concept.

Antimicrobial therapy based on self-assembling peptides.

The emergence of drug-resistant microorganisms has threatened global health, and microbial infections have severely limited the use of medical materials. For example, the attachment and colonization of pathogenic bacteria to medical implant materials can lead to wound infections, inflammation and complications, as well as implant failure, shortening their lifespan and even resulting in patient death. In the era of antibiotic resistance, antimicrobial drug discovery needs to prioritize unconventional therapies that act on new targets or adopt new mechanisms. In this regard, supramolecular antimicrobial peptides have emerged as attractive therapeutic platforms, both as bactericides for combination antibiotics and as delivery vehicles. By taking advantage of their programmable intermolecular and intramolecular interactions, peptides can be modified to form higher-order structures (including nanofibers and nanoparticles) with unique functionality. This paper begins with an analysis of the relationship between peptide self-assembly and antimicrobial activity, describes in detail the research and development of various self-assembled antimicrobial peptides in recent years, and finally explores different combinatorial strategies for self-assembling antimicrobial peptides.

Evaluation of Anti-bacterial Activity Induced by Penicillium mallochii in the Hemolymph of Ephestia kuehniella Zeller (Lepidoptera: Pyralidae)

Anti-microbial peptides (AMPs) exhibit anti-bacterial, anti-fungal and anti-parasite activity and are essential effectors for the immune response of insects. Insect hemolymph contains AMPs, which are one of the sources of antibiotics effective on drug-resistant microorganisms. This study was conducted to induce antimicrobial activity in hemolymph by topical application of different doses of Penicillium mallochii conidia and its metabolite to Ephestia kuehniella larvae. Tetracycline antibiotic disks (TE-10 µg, Sigma), Sulfametaxozole trimethoprim (SXT-25 µg, Sigma), PBS, sterile water, and non-induced hemolymphs of larvae were used as control groups. In total hemolymph induced with metabolite extract, 24-h application was determined to be more effective on test bacteria than 48-h application. The largest zone diameter was observed against Escherichia coli (20mm) in hemolymph collected 24 h after metabolite application. Antimicrobial activity was highly increased (24h and 48h) when larvae were induced with P. mallochii conidial suspension. The largest zone diameter was observed against Proteus vulgaris and Klebsiella pneumonia (20 and 24 mm) in hemolymph collected 24 h after conidial suspension application. When larvae were induced with fungus metabolite and conidia, the zone of inhibition was 1.5-2.5-fold larger than that of the control hemolymph, indicating a higher antimicrobial activity after application. In general, this study provides a novel contribution to the knowledge regarding enhancement of antimicrobial activity in response to fungal infections in larvae.

Antimicrobial Photodynamic Therapy (Apdt), An Approach To Fightback Against Antibiotic Resistance: A Short Review

Antimicrobial photodynamic therapy (APDT), a novel tool for combating the drug resistant microorganisms which is combined with modern technologies and tools. The versatile and wide range of available photosensitizers (PS) and different wavelength light combinations opened so many ways to kill potential disease-causing pathogens. The research is developing so fast with the help of photochemistry, photobiology and photophysics. This is the beginning of new era of another antimicrobial solutions compared to conventional antibiotics. Many articles have published regarding studies on APDT and its applications. This method has shown successful eliminations of pathogenic microorganisms in skin, dental and foot infections as well as tumor or cancer treatment. The findings shared the knowledge of safe and resistance free alternative treatment of antibiotics which has clinical importance globally. This review highlights the concept, history, mechanisms, applications and the advantages of APDT.
 Stamford Journal of Microbiology, 2023. Vol. 13, Issue 1, p. 30-37

Beyond the Virus: Exploring Coinfections in the COVID-19 Pandemic

The global impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, cannot be understated. Amidst the relentless focus on this viral adversary, we must not lose sight of an equally formidable challenge – the lurking threat of bacterial coinfections that can exacerbate morbidity and mortality. Various factors, including ICU admissions, age demographics, microbiota disturbances, and empirical antibiotic use, contribute to the specter of bacterial coinfections. Respiratory tract coinfections, often featuring Streptococcus pneumoniae, precede bacteremia and urinary tract involvement. However, the bacterial landscape in COVID-19 coinfections is a diverse tapestry with regional and institutional variations. Unlike its viral counterparts, COVID-19 exhibits a lower incidence of bacterial coinfection, underscoring the urgency of judicious antibiotic administration to curb the looming threat of antimicrobial resistance. Pandemics have historically witnessed an upsurge in coinfection-related morbidity and mortality. This comprehensive review delves into the multifaceted realm of bacterial, viral, and fungal coinfections amidst the COVID-19 pandemic. We scrutinize their impact on the respiratory and urinary tracts, blood, microbiota, and the ominous emergence of drug-resistant microorganisms. In conclusion, we explore nuanced treatment strategies in the quest for effective pandemic management.

Impact of intestinal colonization by Gram-negative bacteria on the incidence of bloodstream infections and lethality in critically ill neonates

BackgroundEarly detection of antimicrobial-resistant microorganisms is crucial to prevent subsequent invasive infections and contain their spread in the Neonatal Intensive Care Unit (NICU). This study aims to investigate the association between intestinal colonization (IC) by Gram-negative bacteria and the risk of bloodstream infection (BSI) in critically ill neonates. MethodsData from the electronic medical records of 678 newborns admitted to a NICU Brazilian between 2018 and 2022 were retrospectively analyzed. Participants were monitored by the National Health Security Network. ResultsAmong neonates, 6.9 % had IC (56.9 % attributed to Acinetobacter baumannii); of these, 19.1 % developed BSI (66.7 % by Staphylococcus spp.). Within the A. baumannii colonization, 34.5 % occurred during an outbreak in September 2021. Colonized individuals had a longer mean length of stay (49.3 ± 26.4 days) and higher mortality rate (12.8 %) compared to non-colonized individuals (22.2 ± 16.9 days; 6.7 %, respectively). Previous use of antimicrobials and invasive devices significantly increased the risk of colonization. Colonization by drug-resistant microorganisms, along with the occurrence of BSI, was associated with increased mortality and reduced survival time. ConclusionsIC contributed to the incidence of BSI, leading to more extended hospital stays and higher mortality rates. Its early detection proved to be essential to identify an outbreak and control the spread of resistant microorganisms within the NICU.

Benefits of Manuka Honey in the Management of Infectious Diseases: Recent Advances and Prospects.

The benefits of honey have been recognized since ancient times for treating numerous diseases. However, in today's modern era, the use of traditional remedies has been rapidly diminishing due to the complexities of modern lifestyles. While antibiotics are commonly used and effective in treating pathogenic infections, their inappropriate use can lead to the development of resistance among microorganisms, resulting in their widespread prevalence. Therefore, new approaches are constantly required to combat drug-resistant microorganisms, and one practical and useful approach is the use of drug combination treatments. Manuka honey, derived from the manuka tree (Leptospermum scoparium) found exclusively in New Zealand, has garnered significant attention for its biological potential, particularly due to its antioxidant and antimicrobial properties. Moreover, when combined with antibiotics, it has demonstrated the ability to enhance their effectiveness. In this review, we delve into the chemical markers of manuka honey that are currently known, as well as detail the impact of manuka honey on the management of infectious diseases up to the present.

ASSESSMENT OF SHIFT IN THE ANTIBIOTIC SUSCEPTIBILITY PATTERN OF AEROBIC BACTERIAL ISOLATES FROM MICROBIAL BIOFILMS IN PATIENTS WITH ORAL SQUAMOUS CELL CARCINOMA AND PRECANCEROUS CONDITIONS

Background: Antimicrobial resistance is a concerning global health problem in reference to cancer patients as they are more susceptible to drug-resistant microorganisms because of their immunocompromised states. Aim: The aim of this study was to study the changes in the pattern of aerobic bacterial flora in the patients of oral cancer and precancerous lesions and to identify the susceptibility to commonly used Antibiotics in clinical practice. Methods: This prospective observational study was carried out in a randomly selected cohort of oral cancer and precancerous patients being treated at tertiary care centre in Rajasthan, for a period of 1 year. Oral swabs were collected from patients presenting with oral cancer and precancerous lesions and subjected to microbiological examination for their colony characters, morphology on Gram stain as well for Antibiotic sensitivity patterns for commonly used drugs. Results: Of the 100 oral cancer patients, isolated bacterial colonies showed a mixture of Gram-Positive and Gram-Negative organisms. Staphylococcus species (n = 15) were seen in high numbers in the case of Gram-positive organisms, while in Gram-negative bacteria Pseudomonas species (n = 45) increased in number. Among the precancerous patient group normal commensal (Micrococci, n= 24) was the predominant species. In Gram-negative bacteria, all were susceptible to Piperacillin Tazobactam and Imipenem while in Gram-positive bacteria all were susceptible to Linezolid, Gentamicin, and Vancomycin. Conclusion: This study showed 90% susceptibility to every class of commonly used antibiotics. Multidrug resistance (MDR) was seen in 9.52% of the bacterial isolates. Antimicrobial resistance is emerging among cancer patients. Studies on cultural sensitivity patterns will help clinicians to prescribe antibiotics judiciously and will further decrease the chances of antimicrobial resistance in these patients.

Genomic and Proteomic Analysis of Pseudomonas aeruginosa Isolated from Industrial Wastewater to Assess Its Resistance to Antibiotics

Industrial wastewater usually contains a large amount of organic and inorganic pollutants, and many microorganisms. However, the types of microorganism present in industrial wastewater are still unclear. The aim of this study was to analyze the physicochemical properties and drug resistance of Pseudomonas aeruginosa isolated from industrial wastewater containing high concentrations of sulfate compounds. Pseudomonas aeruginosa was isolated from industrial wastewater from industrial produce with high concentrations of sulfate and phosphate, and mass spectrometry identification, gene identification, biochemical analysis and genomic and proteomic property identification were carried out. According to the results of matrix-assisted flight mass spectrometry and 16S rDNA sequencing, the isolated bacterium was identified as Pseudomonas aeruginosa, and was positive for reactions of ONPG, ACE, GLU, MNE, etc. Through growth experiments, it can be seen that Pseudomonas aeruginosa had a significant growth rate in the LB medium. Antibiotic sensitivity tests showed that Pseudomonas aeruginosa was susceptible to most antibiotics and moderately resistant to Polymyxin B and Polymyxin E. The drug resistance gene experiment showed that Pseudomonas aeruginosa had the gyrB gene related to antibiotic resistance. Proteomic analysis revealed that six proteins were involved in antibiotic resistance. This experiment isolated Pseudomonas aeruginosa from industrial produce wastewater containing high concentrations of sulfate and phosphate ions, providing a new perspective for further research on the characteristics and drug resistance of microorganisms in industrial wastewater and their potential functions when using them to deal with environmental pollution.

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. β-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (β- and hydroxy propyl β-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-β- and hydroxy propyl β-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6')-Ib. The blaIMP and aac (6')-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.