Emergence Of Multidrug-resistant Bacteria Research Articles

Antibacterial and antibiofilm properties of two cyclic dipeptides produced by a new desert Streptomyces sp. HG-17 strain against multidrug-resistant pathogenic bacteria.

The emergence of multidrug-resistant bacteria and biofilms requires discovering new antimicrobial agents from unexplored environments. This study aims to isolate and characterize a new actinobacterial strain from the Hoggar Mountains in southern Algeria and evaluate its ability to produce bioactive molecules with potential antibacterial and antibiofilm activities. A novel halotolerant actinobacterial strain, designated HG-17, was isolated from the Hoggar Mountains, and identified based on phenotypic characterizations, 16S rDNA sequence analysis, and phylogenetic analysis. The antibacterial and antibiofilm activities of the strain were assessed, and the presence of biosynthetic genes (PKS-I and NRPS) was confirmed. Two active compounds, HG-7 and HG-9, were extracted butanol solvent, purified by HPLC, and their chemical structures were elucidated using ESI mass spectrometry and NMR spectroscopy. The strain HG-17 was identified as Streptomyces purpureus NBRC with 98.8% similarity. It exhibited strong activity against multidrug-resistant and biofilm-forming bacteria. The two purified active compounds, HG-7 and HG-9, were identified as cyclo-(d-cis-hydroxyproline-l-phenylalanine) and cyclo-(l-prolone-l-tyrosine), respectively. The minimum inhibitory concentrations (MICs) of HG-7 and HG-9 ranged from 3 to 15 μg/mL, comparable to the MICs of tetracycline (8 to 15 μg/mL). Their minimum biofilm inhibitory concentration (MBIC 50%) showed good inhibition from 48.0 to 52.0% at concentrations of 1 to 7 μg/mL against the tested bacteria. This is the first report of cyclo-(d-cis-hydroxyproline-l-phenylalanine) and cyclo-(l-prolone-l-tyrosine) antibiotics from S. purpureus and their anti-multi-drug-resistant and biofilm-forming bacteria. These results indicate that both antibiotics could be used as effective therapeutics to control infections associated with multidrug-resistant bacteria.

Novel biaryloxazolidinone derivatives with broad-spectrum antibacterial activity, favorable drug-like profiles and in vivo efficacy against linezolid-resistant Staphylococcusaureus

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC=0.06μg/mL), MSSA (MIC=0.125μg/mL), MRSA (MIC=0.06μg/mL), LRSA (MIC=0.125μg/mL) and LREFa (MIC=0.5μg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49h, high peak plasma concentration (Cmax=2320ng/mL), high plasma exposure (AUC0-t=8310hng/mL), and superior oral bioavailability (F=68.1%) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.

Recombinant lactococcal-based oral vaccine for protection against Streptococcus agalactiae infections in tilapia (Oreochromis niloticus)

Streptococcosis outbreaks caused by Streptococcus agalactiae infection in tilapia aquaculture have been consistently reported and associated with high mortality and morbidity leading to significant economic losses. Existing vaccine candidates against Streptococcus spp. are designed for intraperitoneal injections that are not practical and labor-intensive which have prompted farmers to protect aquatic animals with antibiotics, thus encouraging the emergence of multidrug resistant bacteria. In this study, a live recombinant L. lactis vaccine expressing a 1403 bp surface immunogenic protein (SIP) and a 1100 bp truncated SIP (tSIP) gene was developed and evaluated against S. agalactiae infection in tilapia. Both SIP and tSIP sequences were cloned and transformed into L. lactis. The recombinant L.lactis vaccine was orally administered to juvenile tilapia for a month. Detection of SIP-specific serum IgM in vaccinated groups compared to control groups indicated that recombinant proteins expressed from L. lactis could elicit immunogenic reactions in tilapia. Fish immunized with the tSIP vaccine also showed the highest level of protection compared to other test groups, and the mortality rate was significantly reduced compared to both control groups. The relative percentage of survival (RPS) against S. agalactiae for both SIP and tSIP-vaccinated groups was 50 % and 89 %, respectively, at 14 days post-challenge. Significant up-regulation of IgM, IL-1β, IL-10, TNF-α and IFN-γ were observed at day 34 between the vaccinated and control groups. These results indicated that the recombinant lactococcal tSIP vaccine can elicit both cell-mediated and humoral responses and is recommended as a potential oral vaccine against S. agalactiae infection. Future work will include further in vivo challenge assessments of this vaccine candidate fused with adjuvants to boost immunogenicity levels in tilapia.

Exploring the efficacy of tryptone-stabilized silver nanoparticles against respiratory tract infection-causing bacteria: a study on planktonic and biofilm forms

Respiratory tract infections (RTIs) are a common cause of mortality and morbidity in the human population. The overuse of antibiotics to overcome such infections has led to antibiotic resistance. The emergence of multidrug resistant bacteria is necessitating the development of novel therapeutic techniques in order to avoid a major global clinical threat. Our study aims to investigate the potential of tryptone stabilised silver nanoparticles (Ts-AgNPs) on planktonic and biofilms produced by Klebsiella pneumoniae (K. pneumoniae) and Pseudomonas aeruginosa (P. aeruginosa). The MIC50 of Ts-AgNPs was found to be as low as 1.7 μg ml−1 and 2.7 μg ml−1 for K. pneumoniae and P.aeruginosa respectively. Ts-AgNPs ability to alter redox environment by producing intracellular ROS, time-kill curves showing substantial decrease in the bacterial growth and significantly reduced colony forming units further validate its antimicrobial effect. The biofilm inhibition and eradication ability of Ts-AgNPs was found to be as high as 93% and 97% in both the tested organisms. A significant decrease in the eDNA and EPS quantity in Ts-AgNPs treated cells proved its ability to successfully distort the matrix and matured biofilms. Interestingly Ts-AgNPs also attenuated QS-induced virulence factors production. This study paves way to develop Ts-AgNPs as novel antibiotics against RTIs causing bacterial biofilms.

Selective inhibitory activity of multidrug-resistant bacteria by zinc oxide nanoparticles

The emergence of multidrug-resistant bacteria has attracted much attention from the global community due to their potential to cause harm to health. In this context, ZnO nanoparticles (NPs) produced under different synthesis conditions were successfully applied to inhibit several species of multiresistant bacteria from clinical isolates. Five gram-positive (Staphylococcus epidermidis ATCC 35984, Staphylococcus aureus ATCC 25923, S. aureus ATCC 8095, Enterococcus faecalis ATCC 29212, and Enterococcus faecium ATCC 700221) and four gram-negative bacterial isolates (Klebsiella pneumoniae ATCC 700603, Escherichia coli ATCC 25922, Acinetobacter baumannii ATCC 19606, and Pseudomonas aeruginosa ATCC 27853), known to be involved in healthcare-associated infections and multidrug resistance, were selected for this study. Due to their physicochemical properties, we found that ZnO NPs can exhibit selective inhibition. The minimum inhibitory concentration (MIC) for multidrug-resistant bacteria sensitive to ZnO NPS was determined from varying contact time and catalyst concentration from exhaustive tests. Different characterization techniques were studied to determine the crystalline, optical, morphological, and photocatalytic characteristics of ZnO NPs. The bacterial inhibition mechanisms were discussed in detail with support of photocatalytic assays and cytotoxicity of plant species. In addition, ZnO NPs have also shown great potential for application in the environmental remediation of ecosystems contaminated by organic pollutants due to their efficiency in degrading the dye methylene blue (MB) under UV light with a photocatalytic efficiency of 75% in 60 min. The ZnO NPs showed great potential for multidrug-resistant bacteria, with MICs ranging from 256 to 512 mg/L. This demonstrates that the ZnO NPs produced here have the potential to be used as a technology with great application potential in materials used in hospital environments to mitigate the growth and development of these classes of multi-resistant bacteria.

Antibacterial type-II InP/ZnO quantum dots via multimodal reactive oxygen species

The emergence of multidrug-resistant bacteria as a global health threat has necessitated the exploration of alternative treatments to combat bacterial infections. Among these, photocatalytic nanomaterials such as quantum dots (QDs) have shown great promise and type-I QDs have been investigated thus far. In this study, we introduce type-II InP/ZnO core/shell QDs that are ligand-exchanged with a short-chain inorganic sulfide ion (S2−) for antibacterial activity. Interestingly, InP/ZnO QDs simultaneously generate reactive oxygen species (ROS) including hydroxyl (•OH) and superoxide (O2•−) radicals, while only O2•− radicals can be released by the type-I sulfide-capped InP/ZnS QDs. The optimized nanostructure achieved effective inhibition of Pseudomonas aeruginosa and Escherichia coli bacteria growth to the level of 99.99% and 70.31% under low-intensity green light illumination of 5 mW.cm−2. Our findings highlight the importance of type-II QDs as a new avenue for developing effective antibacterial agents against drug-resistant pathogens.

Colonization with extended spectrum beta-lactamase and carbapenemases producing Enterobacteriaceae among hospitalized patients at the global level: A systematic review and meta-analysis.

Gut commensal bacteria can mediate resistance against pathogenic bacteria. However, exposure to antibiotics and hospitalization may facilitate the emergence of multidrug resistant bacteria. We aimed to conduct a systematic review and meta-analysis to provide comprehensive evidence about colonization rate of extended spectrum beta-lactamase and carbapenemases producing Enterobacteriaceae. We used PubMed, Google Scholar and Web of Science data bases to search studies from January 1, 2016 to August10, 2022 about colonization rate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae. Data were extracted from eligible studies and analyzed using Stata version 16 software. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools, and publication bias was assessed using funnel plot and eggers test. We identified 342 studies from the comprehensive data search and data were extracted from 20 studies. The pooled estimate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae were 45.6%(95%CI: 34.11-57-10) and 16.19% (95% CI: 5.46-26.91) respectively. The predominant extended spectrum beta-lactamase producers were E. coli,32.99% (95% CI: 23.28-42.69) and K. pneumoniae, 11.43% (95% CI:7.98-14.89). Prolonged hospitalization was linked to carbapenemase producing Enterobacteriaceae colonization with the odds of 14.77 (95% CI: -1.35-30.90) at admission and 45.63 (95% CI: 0.86-92.12) after ≥7 days of admission. The pooled estimate of extended spectrum beta-lactamase and carbapenemase producing Enterobacteriaceae were high. This indicates the need for strong mitigation strategies to minimize the spread of multidrug-resistant bacteria at the healthcare facilities.

New broad-spectrum and potent antibacterial agents with dual-targeting mechanism: Promoting FtsZ polymerization and disrupting bacterial membranes

The emergence of multidrug-resistant bacteria and the slow development of new antibacterial agents have led to a growing global health crisis. Here, we identified an antibacterial agent possessing 1-methyl-2,5-diphenylpyridin-1-ium core, MA220607, with a dual-targeting mechanism of action (MOA), which exhibited effective killing activity against both Gram-positive (MIC = 0.062–2 μg/mL) and Gram-negative bacteria (MIC = 0.5–4 μg/mL). Moreover, our study revealed that MA220607 could block the formation of bacterial biofilm, which might be the reason for low frequency of resistance. MOA studies showed that MA220607 not only promoted FtsZ protein polymerization, but also increased the permeability of bacterial membranes and altered their proton gradients. In addition, MA220607 had low hemolytic toxicity and could significantly inhibit the growth of bacteria in mice. Molecular dynamics simulations demonstrated that MA220607 could block the transition from the tense (T) to relaxed (R) state of FtsZ protein, thereby perturbing the stepping mechanism of FtsZ protein. Overall, our findings suggest that integrating the dual mechanisms targeting FtsZ protein and cell membranes of bacteria into a single scaffold represents a promising direction for the development of new antibacterial agents.

Design and synthesis of etrasimod derivatives as potent antibacterial agents against Gram-positive bacteria

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents. Inspired by our recent report on the antibacterial activity of etrasimod, an immunomodulating drug candidate, we prepared a series of etrasimod derivatives by varying substituents on the phenyl ring, altering the central tricyclic aromatic ring, and modifying the carboxyl group. From this series of compounds, indole derivative 24f was identified as the most potent antibacterial compound, with the minimum inhibitory concentration (MIC) values between 2.5 and 10 μM against various Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), S. epidermidis and enterococci. Moreover, 24f exhibited rapid bactericidal activity against S. aureus, low toxicity and hemolytic activity, and a synergistic effect with gentamicin against S. aureus, MRSA, and Enterococcus faecalis. Furthermore, it was shown that neither etrasimod nor 24f affects S. aureus cell membranes. Importantly, 24f did not induce resistance in S. aureus, representing a significant improvement compared to etrasimod. Finally, the antibacterial activity of etrasimod and 24f against S. aureus and MRSA was confirmed in vivo in a Caenorhabditis elegans infection model. Taken together, our study highlights the value of etrasimod and its derivatives as potential antibacterial candidates for combating infections caused by Gram-positive bacteria.

Broad-range capsule-dependent lytic Sugarlandvirus against Klebsiella sp.

The emergence of antibiotic-resistant bacteria has become a serious global health threat requiring the development of novel treatments. Klebsiella pneumoniae is an encapsulated bacterium considered a major concern due to its high resistance, prevalence, and mortality rates. Phage therapy has been proposed as a very promising alternative to combat infections by Klebsiella sp. infections. However, most of the Klebsiella phages described so far present a high specificity, infecting one or a few capsular types due to the presence of depolymerases in their genomes, which limits their therapeutic potential. Here, we present three new Klebsiella phages isolated from the environment, vB_Kpn_K7PH164C4, vB_Kpn_K30λ2.2, and vB_Kpl_K32PH164C1, belonging to the family Demerecviridae and the genus Sugarlandvirus. The most important feature of these new Klebsiella phages is their broad host range, especially vB_Kpn_K7PH164C4 and vB_Kpn_K30λ2.2, which infects strains of more than 20 different capsular types, representing the broadest infection range observed for Klebsiella phages. Genomic analysis revealed the presence of three receptor-binding proteins lacking depolymerase domains. Nevertheless, capsule expression is suggested to be a determining factor in phage infectivity, despite the absence of depolymerase activity against capsular components. Our findings hold potential for the development of promising phage-based therapeutics directed against K. pneumoniae.IMPORTANCEThe emergence of multi-drug resistant bacteria is a global health problem. Among them, Klebsiella pneumoniae is considered a high-priority pathogen, making it necessary to develop new therapeutic tools to reduce the bacterial burden in an effective and sustainable manner. Phages, bacterial viruses, are very promising tools. However, phages are highy specific, rendering large-scale therapeutics costly to implement. This is especially certain in Klebsiella, a capsular bacterium in which phages have been shown to be capsular type dependent, infecting one or a few capsular types through specific enzymes called depolymerases. In this study, we have isolated and characterized novel phages with lytic ability against bacteria from a wide variety of capsular types, representing the Klebsiella phages with the widest range of infection described. Remarkably, these broad-range phages showed capsule dependency, despite the absence of depolymerases in their genomes, implying that infectivity could be governed by alternative mechanisms yet to be uncovered.

Bactericidal activity of newly synthesized antimicrobial peptides against methicillin-resistant staphylococcus aureus and biofilm-forming methicillin-resistant staphylococcus aureus

Background: The emergence of multidrug-resistant bacteria (MDRB) poses a significant global challenge for healthcare professionals. Methicillin-resistant Staphylococcus aureus (MRSA), a prominent pathogen responsible for both hospital-acquired (nosocomial) and community-acquired infections, is particularly difficult to treat. Existing treatment options, such as vancomycin, linezolid, or clindamycin, have limitations. Therefore, there is a need for innovative approaches to combat infections caused by drug-resistant organisms. Methods: In this study, we synthesized a novel ultra-short antimicrobial peptide composed of three units of tryptophan and three units of lysine. We evaluated the effectiveness of this peptide against MRSA and MRSA that forms biofilms. Results: Encouraging results demonstrated that the peptide effectively killed both MRSA and biofilm-forming MRSA, while exhibiting low toxicity to human red blood cells. Additionally, our novel peptide showed excellent synergistic effects when combined with vancomycin against MRSA. Furthermore, when combined with levofloxacin and clarithromycin, our peptide exhibited synergistic effects against biofilm-forming MRSA. Conclusions: In conclusion, this study presents a novel ultra-short antimicrobial peptide (USAMP) that holds potential as a new generation of antibiotics to combat globally prevalent drug-resistant bacteria.

Evaluation of the antibacterial potency of Thymus algeriensis essential oil against nosocomial bacterial strains

Introduction. The emergence of multi-drug resistant bacteria, and the toll healthcare-associated infections have been causing globally with the development of human therapy increased the overall interest in alternative natural prevention and treatment strategies. Aromatic extracts generally and essential oils specifically were proposed as potential prevention, or complementary therapy against bacterial infections, especially the nosocomial ones. Objectives. The Thymus genus, with its various species, was subject to investigation worldwide, and this study explored the in-vitro antibacterial activity of the formerly chemically identified Algerian northern central Thymus algeriensis. Method. Three bacterial strains were employed (i.e., Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli) based on their prevalence in Algerian health institutions. Results. The analysis revealed the sensitivity of Escherichia coli and Staphylococcus aureus to the essential oil activity, while Pseudomonas aeruginosa was resistant. The results comparison to local and regional research groups’ outputs suggests that Linalool, a major component of the present study essential oil, is a main vector of the antibacterial activity, and its quantitative variation results in drastic activity shifts. Conclusions. This work highlighted the selective sensitivity of Escherichia coli and Staphylococcus aureus to Thymus algeriensis essential oil and insist on the chemical identification of local aromatic species before aromatherapy implementation.

Synthesis, characterization, and antibacterial activity of chitosan-chelated silver nanoparticles

Bacterial infections pose a significant threat to human health and safety, necessitating the urgent resolution of the problem through the development and implementation of highly effective antibacterial agents. However, the emergence of multidrug-resistant bacteria has diminished the satisfactory effectiveness of antibacterial treatments. To overcome this obstacle, we developed effective antibacterial agents by chemical reduction for inhibiting bacterial proliferation and inducing membrane damage. Specifically, four different types of chitosan/Ag nanoparticle (CS-AgNPs-i) (i-1, 2, 3, 4) complexes were synthesized by varying the quantity of chitosan added during the synthesis process. We found that the amount of CS does not affect the morphology and size of CS-AgNPs-i, which remained at approximately 20 nm and all CS-AgNPs were mostly spherical. The zeta potential measurements indicated that the surface of CS-AgNPs carries a positive charge. Notably, elevating the chitosan concentration led to a more pronounced antibacterial impact, particularly evident in its interaction with the peptidoglycan layer on the bacterial surface. Our experimental results undeniably establish the potent antibacterial efficacy of CS-AgNPs against both Escherichia coli and Staphylococcus aureus. Employing live/dead bacterial staining, we reveal the marked capability of CS-AgNPs to effectively hinder bacterial proliferation. Furthermore, our experimental investigations revealed that CS-AgNPs possess broad-spectrum antimicrobial activity. The results of in vitro cytotoxicity experiments substantiated the high biocompatibility of CS-AgNPs with elevated chitosan loading. The study provides valuable insights into the development of nano-antibacterial agents that exhibit significant potential as a substitute to replace traditional antibiotics for medical applications.

A risk assessment framework for multidrug-resistant Staphylococcus aureus using machine learning and mass spectrometry technology.

The emergence of multidrug-resistant bacteria is a critical global crisis that poses a serious threat to public health, particularly with the rise of multidrug-resistant Staphylococcus aureus. Accurate assessment of drug resistance is essential for appropriate treatment and prevention of transmission of these deadly pathogens. Early detection of drug resistance in patients is critical for providing timely treatment and reducing the spread of multidrug-resistant bacteria. This study aims to develop a novel risk assessment framework for S. aureus that can accurately determine the resistance to multiple antibiotics. The comprehensive 7-year study involved ˃20000 isolates with susceptibility testing profiles of six antibiotics. By incorporating mass spectrometry and machine learning, the study was able to predict the susceptibility to four different antibiotics with high accuracy. To validate the accuracy of our models, we externally tested on an independent cohort and achieved impressive results with an area under the receiver operating characteristic curve of 0. 94, 0.90, 0.86 and 0.91, and an area under the precision-recall curve of 0.93, 0.87, 0.87 and 0.81, respectively, for oxacillin, clindamycin, erythromycin and trimethoprim-sulfamethoxazole. In addition, the framework evaluated the level of multidrug resistance of the isolates by using the predicted drug resistance probabilities, interpreting them in the context of a multidrug resistance risk score and analyzing the performance contribution of different sample groups. The results of this study provide an efficient method for early antibiotic decision-making and a better understanding of the multidrug resistance risk of S. aureus.

A Novel Antimicrobial Peptide, Dermaseptin-SS1, with Anti-Proliferative Activity, Isolated from the Skin Secretion of Phyllomedusa tarsius.

The emergence of multidrug-resistant bacteria has severely increased the burden on the global health system, and such pathogenic infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly attracting great interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin-secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a 'shotgun' cloning strategy. The chemically synthesized peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed lower salt sensitivity and more rapid bacteria killing compared to SS1. Both peptides employed a membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues against lung cancer cell lines was found to be significant.

Early Intra-Abdominal Bacterial Infections after Orthotopic Liver Transplantation: A Narrative Review for Clinicians.

Despite recent advances in the transplant field, infectious complications after orthotopic liver transplantation (OLT) are major causes of morbidity and mortality. Bacterial intra-abdominal infections (IAIs) are predominant during the first month post-transplantation and affect patient and graft survival. Recently, the emergence of multidrug resistant bacteria has generated great concern in OLT patients. We performed this narrative review of the literature in order to propose a "ready-to-use" flowchart for reasoned empirical antibiotic therapy in the case of suspected post-OLT IAIs. The review was ultimately organized into four sections: "Epidemiology and predisposing factors for IAI"; "Surgical-site infections and perioperative prophylaxis"; "MDRO colonization and infections"; and "Reasoned-empirical antibiotic therapy in early intra-abdominal infections post OLT and source control". Multidisciplinary teamwork is warranted to individualize strategies for the prevention and treatment of IAIs in OLT recipients, taking into account each patient's risk factors, the surgical characteristics, and the local bacterial epidemiology.

Identification and anti-bacterial property of endophytic actinobacteria from Thymes kotschyanus, Allium hooshidaryae, and Cerasus microcarpa

The arbitrary and overuses of antibiotics have resulted in the emergence of multidrug resistance bacteria which encounters human to a serious public health problem. Thus, there is an ever-increasing demand for discovery of novel effective antibiotics with new modes of function against resistant pathogens. Endophytic actinobacteria (EA) have currently been considered as one of the most prospective group of microorganisms for discovery of therapeutic agents. This study aimed to isolate EA from Thymes kotschyanus, Allium hooshidaryae, and Cerasus microcarpa plants and to evaluate their antibacterial properties. The healthy samples were collected, dissected and surface-sterilized before cultured on four different selection media at 28 °C. Nine EA were isolated and identified based on morphological and molecular properties, and scanning electron micrograph analyses. Based on phylogenetic analysis, they were taxonomically grouped into four families Streptomycetaceae, Nocardiaceae, Micromonosporaceae, and Pseudonocardiaceae. Their branched aerial mycelia produced chains of cylindrical or cube or oval shaped spores with smooth or rough surfaces. Four strains; IKBG03, IKBG05, IKBG13, and IKBG17 had less than 98.65% sequence similarity to their closely related strains, which constitute them as novel species/strains. Besides, three strains; IKBG05, IKBG13, and IKBG18 were reported as endophytes for the first time. Preliminary antibacterial activity conducted on the all isolates revealed potent antibacterial effects against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. All isolates strongly inhibited the growth of at least one of the tested pathogens. Our results reveals that the test plants are novel sources for isolating a diverse group of rare and common actinobacteria that could produce a wide range of novel biologically active natural products with antibacterial activity which have a great potential in pharmaceutical and biotechnological applications.

Exploring the antimicrobial potential of biologically synthesized zero valent iron nanoparticles

Abstract The widespread use of antibiotics has resulted in the emergence of multidrug-resistant bacteria. Therefore, it is essential to explore alternative strategies to effectively combat medically significant resistant pathogens. In recent years, nanoparticles (NPs) have emerged as a promising alternative source of antimicrobial agents. While nanoscale particles were traditionally synthesized using chemical techniques, the development of metallic NPs using biological methods has garnered attention. This current study focuses on the synthesis of iron NPs (Fe NPs) using metal-tolerant fungal strains, as numerous microorganisms serve as environmentally safe and durable precursors to produce persistent and bi-functional NPs. The study involved the isolation and evaluation of ten fungal strains that are resistant to heavy metals to determine their ability to produce Fe NPs. The biologically synthesized Fe NPs were characterized using X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), and scanning electron microscopy techniques. The XRD results indicated the presence of Fe in nanopowder form, displaying a series of reflection angles (2θ) at 65° and 75° indicating the existence of cubic planes. EDX analysis revealed the presence of ferrous and ferric elements, along with zero-valent Fe NPs. Micrographs of the surface topology displayed spherical aggregation of the synthesized NPs. Furthermore, the Fe NPs exhibited promising antibacterial potential against selected bacterial strains, including Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Cronobacter sakazakii, Listeria innocua, and Enterococcus fecalis. This study demonstrates that the biological synthesis of metallic NPs is environmentally safe, and Fe NPs produced through mycological means could be utilized to combat antibiotic-resistant pathogenic strains.

Study of Structurally Diverse Currently Used and Recently Developed Antimycobacterial Drugs.

Despite major antimicrobial therapeutic advancements, widespread use and misuse of antimicrobial drugs have increased antimicrobial drug resistance, posing a severe danger to public health. In particular, the emergence of multidrug-resistant bacteria has provided considerable difficulty in the treatment of pathogenic infections. As a result, the creation of novel drugs to treat resistant bacteria is one of the most significant disciplines of antimicrobial research today. TB therapy has recently gained a lot of attention, in addition to developing novel and efficient antibacterial drugs to battle multidrug-resistant illnesses. The use of a different class of drugs, such as well-known drugs, their derivatives, and various new heterocyclic compounds like nitroimidazoles, imidazole analogues, triazoles, imidazopyridines, quinolines, purines, as well as thioactomycin, mefloquine, deazapteridines, benzothiadiazine and other molecules such as benzoxazines, diterpenoids, tryptanthin and phenazine and toluidine analogues followed by many other classes of compounds and their effects are also discussed. As a result, current and newly found antitubercular drugs and their toxicities and mode of action have been focused.

Individualized antibiotic dosage regimens for patients with augmented renal clearance.

Objectives: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%-65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying mechanisms, and risk factors of ARC to guide individualized dosing of antibiotics and various strategies for optimizing outcomes. Methods: We searched for articles between 2010 and 2022 in the MEDLINE database about ARC patients and antibiotics and further provided individualized antibiotic dosage regimens for patients with ARC. Results: 25 antibiotic dosage regimens for patients with ARC and various strategies for optimization of outcomes, such as extended infusion time, continuous infusion, increased dosage, and combination regimens, were summarized according to previous research. Conclusion: ARC patients, especially critically ill patients, need to make individualized adjustments to antibiotics, including dose, frequency, and method of administration. Further comprehensive research is required to determine ARC staging, expand the range of recommended antibiotics, and establish individualized dosing guidelines for ARC patients.