Acinetobacter Baumannii Strains Research Articles

Imipenem/funobactam (formerly XNW4107) in vivo pharmacodynamics against serine carbapenemase-producing Gram-negative bacteria: a novel modelling approach for time-dependent killing.

Imipenem/funobactam (formerly XNW4107) is a novel β-lactam/β-lactamase inhibitor with activity against MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales strains. Using a neutropenic murine thigh infection model, we aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) index, relative to funobactam exposure, that correlated most closely with the in vivo efficacy of imipenem/funobactam combination and the magnitude of index required for efficacy against serine carbapenemase-producing clinical strains. Dose-fractionation was conducted against three strains. Imipenem human-simulated regimen (HSR, 500 mg q6h 1 h infusion) efficacy in combination with escalating funobactam exposures against seven A. baumannii, four P. aeruginosa and four Klebsiella pneumoniae (imipenem/funobactam MICs 0.25-16 mg/L) was assessed as 24 h change in log10cfu/thigh. Increased funobactam fractionation enhanced efficacy, indicating time-dependent killing. Changes in log10cfu/thigh versus %fT > MIC were poorly predictive of efficacy; bactericidal activity was observed at %fT > MIC = 0%. Across different threshold plasma funobactam concentrations (CTs), %fT > CT(1 mg/L) had the highest correlation with efficacy. Normalizing the %fT > CT = 1 mg/L index to the respective isolate imipenem/funobactam MIC ([%fT > CT]/MIC) allowed integration of the isolate's susceptibility, which further enhanced the correlation. Median (%fT > CT[1 mg/L])/MIC values associated with 1-log reductions were 9.82 and 9.90 for A. baumannii and P. aeruginosa, respectively. Median (%fT > CT[1 mg/L])/MIC associated with stasis was 55.73 for K. pneumoniae. Imipenem/funobactam 500/250 mg q6h 1 h infusion HSR produced >1-log kill against 6/7 A. baumannii, 4/4 P. aeruginosa and stasis against 4/4 K. pneumoniae. Imipenem/funobactam showed potent in vivo efficacy against serine carbapenemase-producers. The novel PK/PD index (%fT > CT)/MIC appeared to best describe in vivo activity.

Antimicrobial susceptibility of ESKAPE pathogens in the SS. Antonio e Biagio e Cesare Arrigo Hospital’s catchment area: December 2021 - July 2022

Background and Aims: this report describes the minimum inhibitory concentration distributions of the main drugs used against ESKAPE pathogens infection, recovered from patients treated between December 2021 and July 2022 at SS. Antonio e Biagio e Cesare Arrigo Hospital. Materials and Methods: data were extracted by a new Laboratory Information System implemented in mid-November 2021. Results: after exclusion of colonization: i) 56% of Enterococcus faecium was susceptible to teicoplanin and vancomycin; ii) 74% of Staphylococcus aureus was susceptible to methicillin; iii) 55.3% of Klebsiella pneumoniae was susceptible to cefotaxime, ceftazidime and cefepime and 93.2% of KPC was susceptible to ceftazidime/avibactam; iv) no Acinetobacter baumannii strains were resistant to colistin; v) 88.9% of Pseudomonas aeruginosa was susceptible to ceftolozane/tazobactam and 92.2% to ceftazidime/avibactam; vi) among Enterobacter species, 84.6% was susceptible to cefepime and 87.1% to ciprofloxacin. Conclusions: periodic reporting of local antibiotic resistance is an adjunctive tool to help the choice of antimicrobial therapy.

Extensive Drug Resistance of Strong Biofilm-Producing Acinetobacter baumannii Strains Isolated from Infections and Colonization Hospitalized Patients in Southern Poland.

Acinetobacter baumannii (AB) is a bacterium that causes infections, particularly in immunocompromised patients. Treatment is challenging due to biofilm formation by AB strains, which hinders antibiotic effectiveness and promotes drug resistance. The aim of our study was to analyze the biofilm-producing capacity of AB isolates from various forms of infections in relation to biofilm-related genes and their drug resistance. We tested one hundred isolates for biofilm formation using the crystal violet microplate method. Drug resistance analyses were performed based on EUCAST and CLSI guidelines, and biofilm genes were detected using PCR. All tested strains were found to form biofilms, with 50% being ICU strains and 72% classified as strong biofilm producers. Among these, 87% were extensively drug-resistant (XDR) and 2% were extra-extensively drug-resistant (E-XDR). The most common gene set was bap, bfmS, csuE, and ompA, found in 57% of all isolates. Our research shows that, regardless of the form of infection, biofilm-forming strains can be expected among AB isolates. The emergence of E-XDR and XDR strains among non-ICU infections highlights the necessity for the rational use of antibiotics to stop or limit the further acquisition of drug resistance by A. baumannii.

Assesment of polyphenolic compounds against biofilms produced by clinical Acinetobacter baumannii strains using in silico and in vitro models

Several types of microbial infections are caused by Acinetobacter baumanii that has developed resistance to antimicrobial agents. We therefore investigated the role of plant polyphenols against A. baumannii using in silico and in vitro models. The clinical strains of A. baumannii were investigated for determination of resistance pattern and resistance mechanisms including efflux pump, extended spectrum beta lactamase, phenotype detection of AmpC production, and Metallo-β-lactamase. The polyphenolic compounds were docked against transcription regulator BfmR (PDB ID 6BR7) and antimicrobial, antibiofilm, and anti-quorum sensing activities were performed. The antibiogram studies showed that all isolated strains were resistant. Strain A77 was positive in Metallo-β-lactamase production. Similarly, none of strains were producers of AmpC, however, A77, A76, A75 had active efflux pumps. Molecular docking studies confirmed a strong binding affinity of Rutin and Catechin towards transcription regulator 6BR7. A significant antimicrobial activity was recorded in case of quercetin and syringic acid (MIC 3.1 µg/mL) followed by vanillic acid and caffeic acid (MIC 12.5 µg/mL). All tested compounds presented a strong antibiofilm activity against A. baumanii strain A77 (65 to 90%). It was concluded that all tested polyphenols samples posess antimicrobial and antibiofilm activities, and hence they may be utilized to treat multidrug resistance A. baumannii infections.

Amphiphilic peptide Mastoparan-B induces conformational changes within the AdeB efflux pump, down-regulates adeB gene expression, and restores antibiotic susceptibility in an MDR strain of Acinetobacter baumannii.

Mastoparan B (MP-B) is an amphiphilic peptide with a potent antimicrobial activity against most Gram-negative bacteria. However, there is little information available on the inhibition of the Acinetobacter baumannii resistance-nodulation-cell-division (RND) efflux pump using this antimicrobial peptide. Here, we carried out a series of in-silico experiments to find the mechanisms underlying the anti-efflux activity of MP-B using a multi-drug resistant (MDR) strain of A. baumannii (AB). According to our findings, MP-B demonstrated a potent antibacterial activity against an MDR-AB (minimum inhibitory concentration [MIC] = 1 μg/mL) followed by a 20-fold reduction in the adeB gene expression in the presence of sub-MIC of this peptide. Using Groningen Machine for Chemicals Simulation (GROMACS)via PyMOL Graphical User Interface (GUI), (we observed that, the AdeB transporter had conserved helix-turn-helix regions and a tight pore rich in Phe and Ala residues. To understand how inhibition of the AdeB is achieved, we generated 20 apo-MP-B poses using the InterPep and SiteMap tools. The high-quality model was created by homology modeling and used for docking via AutoDock/Vina to identify the MP-B binding sites. We established that the most apo-MP-B formed H-bonds to the backbone of five amino acids in the Helix-5. As a result, the dihedral angles of the involved amino acids shift by 9.0-9.6 Ǻ, causing a change in the conformation of the AdeB protein. This led to helix conformation stereoisomerization and block the AdeB activity. MP-B presumably has dual mechanisms. (1) It blocks the AdeB transporter by changing its conformation. (2) MP-B influences the adeB gene expression by binding to G-protein which laterally controls efflux regulators like MarA, RamA, SoxS, and Rob proteins.

Genome Sequence of Clinical Acinetobacter baumannii Strain V15.

Acinetobacter baumannii is recognized as a critical human pathogen by the World Health Organization, and therefore there is increasing interest in studying its biology and pathophysiology. Among other strains, A. baumannii V15 has been extensively used for these purposes. Here, the genome sequence of A. baumannii V15 is presented.

TonB-Dependent Receptor Protein Displayed on Spores of Bacillus subtilis Stimulates Protective Immune Responses against Acinetobacter baumannii.

The emergence of antibiotic-resistant Acinetobacter baumannii strains with limited treatment options has become a significant global health concern. Efforts to develop vaccines against the bacteria have centred on several potential protein targets, including the TonB-dependent receptors (TBDRs). In the present study, TBDRs from A. baumannii were displayed on the surface of Bacillus subtilis spores. The immunogenicity of the recombinant spores was evaluated in orally vaccinated mice. None of the immunized mice demonstrated signs of illness and were observed to be healthy throughout the study. Sera and the intestinal secretions from the recombinant spores-treated mice demonstrated mucosal and humoral antibody responses to the vaccine antigen. In addition, bactericidal activities of the sera against A. baumannii clinical isolates were demonstrated. These observations suggest that the B. subtilis spore-displayed TBDRs should be further explored as much-needed potential oral vaccine candidates against A. baumannii.

Antimicrobial peptide-loaded decellularized placental sponge as an excellent antibacterial skin substitute against XDR clinical isolates.

Post-wound infections have remained a serious threat to society and healthcare worldwide. Attempts are still being made to develop an ideal antibacterial wound dressing with high wound-healing potential and strong antibacterial activity against extensively drug-resistant bacteria (XDR). In this study, a biological-based sponge was made from decellularized human placenta (DPS) and then loaded with different concentrations (0, 16µg/mL, 32µg/mL, 64µg/mL) of an antimicrobial peptide (AMP, CM11) to optimize an ideal antibacterial wound dressing. The decellularization of DPS was confirmed by histological evaluations and DNA content assay. The DPS loaded with different contents of antimicrobial peptides (AMPs) showed uniform morphology under a scanning electron microscope (SEM) and cytobiocompatibility for human adipose tissue-derived mesenchymal stem cells. Antibacterial assays indicated that the DPS/AMPs had antibacterial behavior against both standard strain and XDR Acinetobacter baumannii in a dose-dependent manner, as DPS loaded with 64µg/mL showed the highest bacterial growth inhibition zone and elimination of bacteria under SEM than DPS alone and DPS loaded with 16µg/mL and 32µg/mL AMP concentrations. The subcutaneous implantation of all constructs in the animal model demonstrated no sign of acute immune system reaction and graft rejection, indicating in vivo biocompatibility of the scaffolds. Our findings suggest the DPS loaded with 64µg/mL as an excellent antibacterial skin substitute, and now promises to proceed with pre-clinical and clinical investigations.

Replicative Acinetobacter baumannii strains interfere with phagosomal maturation by modulating the vacuolar pH.

Bacterial pneumonia is a common infection of the lower respiratory tract that can afflict patients of all ages. Multidrug-resistant strains of Acinetobacter baumannii are increasingly responsible for causing nosocomial pneumonias, thus posing an urgent threat. Alveolar macrophages play a critical role in overcoming respiratory infections caused by this pathogen. Recently, we and others have shown that new clinical isolates of A. baumannii, but not the common lab strain ATCC 19606 (19606), can persist and replicate in macrophages within spacious vacuoles that we called Acinetobacter Containing Vacuoles (ACV). In this work, we demonstrate that the modern A. baumannii clinical isolate 398, but not the lab strain 19606, can infect alveolar macrophages and produce ACVs in vivo in a murine pneumonia model. Both strains initially interact with the macrophage endocytic pathway, as indicated by EEA1 and LAMP1 markers; however, the fate of these strains diverges at a later stage. While 19606 is eliminated in an autophagy pathway, 398 replicates in ACVs and are not degraded. We show that 398 reverts the natural acidification of the phagosome by secreting large amounts of ammonia, a by-product of amino acid catabolism. We propose that this ability to survive within macrophages may be critical for the persistence of clinical A. baumannii isolates in the lung during a respiratory infection.

Egg-yolk antibodies raised to VacJ passively immunize mice against Acinetobacter baumannii pneumonia in a neutropenic murine model

There is no effective antibiotic against emerging highly resistant Acinetobacter baumannii strains, and there is a need for alternative treatment options. Egg-yolk antibodies (IgYs) are the avian equivalent of mammalian IgG that could confer passive protection against various infections. VacJ is a virulence factor of the pathogen in the lungs. In addition, previous studies have shown that immunization of mice with this antigen resulted in decreased bacterial burden in the lung. Hence, it could be a suitable antigen to achieve protective IgYs. In the current study, the recombinant VacJ was expressed, purified, and administered to laying White Leghorn hens followed by IgY extraction from egg yolks. Indirect ELISA showed maximum IgY titers against VacJ raised two weeks following the last immunization. The immunoprotective effects of IgYs were investigated in neutropenic mice. The mice received intranasal IgYs one hour before the nasal instillation of the 10 ×LD50 with a clinical isolate of A. baumannii. A significant reduction in bacterial population loaded in the lungs and spleen was noted. A 100% survival was recorded in the group receiving anti-VacJ antibodies. The results indicate that VacJ is a good immunogen for the production of anti-A. baumannii IgY.

Genome-wide identification and oxacillinase OXA distribution characteristics of Acinetobacter spp. based on a global database.

To use genomic analysis to identify Acinetobacter spp. and to explore the distribution characteristics of ß-lactamase oxallicinases (blaOXA) among Acinetobacter species globally. Genomes of global Acinetobacter spp. were downloaded from GenBank using Aspera batch. After quality check using CheckM and QUAST software, the genomes were annotated using Prokka software to investigate the distribution of blaOXAs across Acinetobacter spp.; a phylogenetic tree was constructed to explore the evolutionary relationship among the blaOXA genes in Acinetobacter spp. Average-nucleotide identification (ANI) was performed to re-type the Acinetobacter spp. BLASTN comparison analysis was implemented to determine the sequence type (ST) of Acinetobacter baumannii strain. A total of 7,853 genomes were downloaded, of which only 6,639 were left for further analysis after quality check. Among them, 282 blaOXA variants were identified from the genomes of 5,893 Acinetobacter spp.; blaOXA-23 (n = 3,168, 53.8%) and blaOXA-66 (2,630, 44.6%) were the most frequent blaOXAs, accounting for 52.6% (3,489/6639), and the co-carriage of blaOXA-23 and blaOXA-66 was seen in 2223 (37.7%) strains. The 282 blaOXA variants were divided into 27 clusters according to the phylogenetic tree. The biggest clade was blaOXA-51-family carbapenem-hydrolyzing enzymes composed of 108 blaOXA variants. Overall, 4,923 A. baumannii were identified out of the 6,639 Acinetobacter spp. strains and 291 distinct STs were identified among the 4,904 blaOXA-carrying A. baumannii. The most prevalent ST was ST2 (n = 3,023, 61.6%) followed by ST1 (n = 228, 4.6%). OXA-like carbapenemases were the main blaOXA-type β-lactamase spread widely across Acinetobacter spp. Both blaOXA-23 and blaOXA-66 were the predominant blaOXAs, among all A. baumannii strains, with ST2 (belonging to CC2) being the main clone disseminated globally.

Clinical Distribution and Drug Resistance of Acinetobacter baumannii in a Hospital from 2019 to 2021

Objective: To analyze the clinical distribution and drug resistance of Acinetobacter baumannii (AB) and provide reference for the treatment of AB infection. Methods: AB isolated from clinical specimens of Huaihua First People’s Hospital from 2019 to 2021 were collected and identified by VITEK 2 Compact, an automated microbial identification and susceptibility testing system, in which drug sensitivity test was also performed. Excel was used for statistical analysis. Results: Among the 1,311 AB strains, 81.16% (1,064 strains) were from sputum samples, and the departments with the highest detections rates of AB were neurosurgery (24.33%), intensive care (15.48%) and infectious disease (11.44%). The drug sensitivity test showed that the resistance rate of 1,311 AB strains to compound sulfamethoxazole and amikacin was 28.38% and 20.54%, respectively, and the resistance rate to 10 other kinds of common antibiotics was more than 40%. Conclusion: The 1,311 AB strains isolated were widely distributed in clinical settings and had strong resistance to commonly used antibiotics. Therefore, it is necessary to strengthen the monitoring of pathogens and drug resistance, formulate reasonable and effective infection control measures, and ensure that antibiotics are used in a reasonable manner.

Prevalence and Phenotypic and Genotypic Patterns of Antibiotic Resistance of Acinetobacter baumannii Strains Isolated from Fish, Shrimp, and Lobster Samples

Acinetobacter baumannii has emerged as a significant hospital pathogen, quickly becoming resistant to commonly prescribed antimicrobials. The present survey was done to evaluate the prevalence, antibiotic resistance pattern, and distribution of antibiotic resistance genes amongst the A. baumannii strains isolated from fish, shrimp, and lobster samples. Four-hundred and fifty seafood samples (100 g each) were collected from Shiraz, Iran. Acinetobacter baumannii was determined using culture and biochemical tests. Pattern of antibiotic resistance and distribution of antibiotic resistance genes were determined using the disk diffusion and polymerase chain reaction, respectively. A. baumannii contamination rate amongst the examined seafood samples was 4.44%, with the higher contamination rate of fish samples (7.85%). A. baumannii isolates harbored the maximum resistance rate against tetracycline (85%), ampicillin (85%), gentamicin (70%), and erythromycin (60%). Resistance rates toward trimethoprim-sulfamethoxazole, ciprofloxacin, ceftazidime, and azithromycin were 55%, 45%, 35%, and 30%, respectively. The minimum rates of resistance were obtained against imipenem (10%) and chloramphenicol (15%). The most commonly detected antibiotic resistance genes were blaCITM (75%), blaSHV (70%), tetA (70%), qnrA (55%), blaVIM (50%), and aac(3)-IV (50%). aadA1, sul1, dfrA1, qnr, blaVIM, blaSIM, blaOXA-51, blaOXA-23, and blaOXA-58 genes were detected in 40%, 30%, 45%, 50%, 35%, 25%, 30%, and 20% of isolates, respectively. The role of seafood samples as a potential reservoirs of antibiotic-resistant A. baumannii strains was determined. However, further investigations are required to identify additional epidemiological features of A. baumannii in seafood samples.

Clinical Outcomes and Associated Factors for Mortality among Pediatric Patients with Carbapenem-Resistant Acinetobacter baumannii

Background: Acinetobacter baumannii bacteremia is a hospital-acquired infection with a high mortality rate. Up to 80% of hospital-acquired A. baumannii infections are caused by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Objective: To determine the overall 30-day mortality rate, factors associated with mortality, and antibiotic drug susceptibility patterns of CRAB isolates among children with hospital-acquired CRAB bloodstream infections. Materials and Methods: A retrospective review was conducted among hospitalized pediatric patients between January 2017 and September 2022 at King Chulalongkorn Memorial Hospital, Bangkok. The inclusion criteria were CRAB bacteremia in children under 18 years of age. Thirty-day mortality after CRAB bacteremia was analyzed using Kaplan-Meier estimates. Associated factors were analyzed by Poisson regression. Antibiotic susceptibility patterns of nine antimicrobial agents were summarized. Results: Fifty-eight patients with 66 episodes of CRAB bacteremia were identified. The median age was 7.5 months (IQR 0.8 to 60.0), and 86.4% of the patients were admitted to the intensive care unit. Central line-associated bloodstream infections (CLABSI) were identified in 90.9% of cases. Most patients (74.2%) received colistin combination with sulbactam regimen. The 30-day mortality rate was 19.7% (95% CI 10.9 to 31.3). Associated factors for mortality rate were septic shock (aRR 7.6, 95% CI 2.3 to 25.0) and underlying congenital heart disease (aRR 3.4, 95% CI 1.0 to 11.7). Drug susceptibility of colistin and tigecycline were 93% and 48%, respectively. Sulbactam was not susceptible. Conclusion: One-fifth of children with CRAB bacteremia died within 30 days. Associated factors with mortality were septic shock and congenital heart disease. Colistin had the highest in vitro drug susceptibility rate. The common regimen used in the present study was colistin combination with sulbactam therapy. Keywords: Acinetobacter baumannii; Bacteremia; Carbapenem resistance; Susceptibility; Mortality; Pediatrics

A CcdB toxin-derived peptide acts as a broad-spectrum antibacterial therapeutic in infected mice.

The bacterial toxin CcdB (Controller of Cell death or division B) targets DNA Gyrase, an essential bacterial topoisomerase, which is also the molecular target for fluoroquinolones. Here, we present a short cell-penetrating 24-mer peptide, CP1-WT, derived from the Gyrase-binding region of CcdB and examine its effect on growth of Escherichia coli, Salmonella Typhimurium, Staphylococcus aureus and a carbapenem- and tigecycline-resistant strain of Acinetobacter baumannii in both axenic cultures and mouse models of infection. The CP1-WT peptide shows significant improvement over ciprofloxacin in terms of its in vivo therapeutic efficacy in treatingestablished infections of S. Typhimurium, S. aureus and A. baumannii. The molecular mechanism likely involves inhibition of Gyrase or Topoisomerase IV, depending on the strain used. The study validates the CcdB binding site on bacterial DNA Gyrase as a viable and alternative target to the fluoroquinolone binding site.

Mobile genetic elements carrying aminoglycoside resistance genes in Acinetobacter baumannii isolates belonging to global clone 2.

Aminoglycosides are used to treat infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. However, resistance to aminoglycosides has increased remarkably in the last few years. Here, we aimed to determine the mobile genetic elements (MGEs) associated with resistance to aminoglycosides in the global clone 2 (GC2) A. baumannii. Among the 315 A. baumannii isolates, 97 isolates were identified as GC2, and 52 of GC2 isolates (53.6%) were resistant to all the aminoglycosides tested. The AbGRI3s carrying armA were detected in 88 GC2 isolates (90.7%), and of them, 17 isolates (19.3%) carried a new variant of AbGRI3 (AbGRI3ABI221). aphA6 was located in TnaphA6 of 30 isolates out of 55 aphA6-harboring isolates, and 20 isolates were found to harbor TnaphA6 on a RepAci6 plasmid. Tn6020 carrying aphA1b was detected in 51 isolates (52.5%), which was located within AbGRI2 resistance islands. The pRAY* carrying the aadB gene was detected in 43 isolates (44.3%), and no isolate was found to contain a class 1 integron harboring this gene. The GC2 A. baumannii isolates contained at least one MGE carrying the aminoglycoside resistance gene, located mostly either in the chromosome within AbGRIs or on the plasmids. Thus, it is likely that these MGEs play a role in the dissemination of aminoglycoside resistance genes in GC2 isolates from Iran.

Identification of an Outbreak Cluster of Extensively Antibiotic-Resistant GC1 Acinetobacter baumannii Isolates in U.S. Military Treatment Facilities.

An outbreak involving an extensively antibiotic-resistant Acinetobacter baumannii strain in three military treatment facilities was identified. Fifty-nine isolates recovered from 30 patients over a 4-year period were found among a large collection of isolates using core genome multilocus sequence typing (MLST). They differed by only 0 to 18 single nucleotide polymorphisms (SNPs) and carried the same resistance determinants except that the aphA6 gene was missing in 25 isolates. They represent a novel sublineage of GC1 lineage 1 that likely originated in Afghanistan. IMPORTANCE A. baumannii is recognized as one of the most important nosocomial pathogens, and carbapenem-resistant strains pose a particularly difficult treatment challenge. Outbreaks linked to this pathogen are reported worldwide, particularly during periods of societal upheaval, such as natural disasters and conflicts. Understanding how this organism enters and establishes itself within the hospital environment is key to interrupting transmission, but few genomic studies have examined these transmissions over a prolonged period. Though historical, this report provides an in-depth analysis of nosocomial transmission of this organism across continents and within and between different hospitals.

Molecular Docking, Anti-Biofilm & Antibacterial Activities and Therapeutic Index of mCM11 Peptide on Acinetobacter baumannii Strains

Despite the huge efforts of microbiologists, infectious diseases have yet remained one of the leading causes of death in humans, further highlighting the research priority for controlling opportunistic pathogens. Many researchers have used antibacterial peptides to solve the problem of antibiotic resistance. This research is thus conducted to investigate the antibacterial and anti-biofilm activity of a novel modified cecropin-melittin 11-peptide with improved therapeutic properties and lower side effects. After synthesis and purification of mCM11 (NH2-WRLFRRILRVL-NH2) by solid-phase synthesis and HPLC methods, respectively, the antibacterial and biofilm inhibitory activities were explored in vitro. TMHMM was used to confirm the reaction of mCM11 on the plasma membrane of the prokaryotic cells. The interaction between mCM11 on Acinetobacter baumannii strains was investigated by molecular docking using ClusPro2.0. Hemolysis and therapeutic indexes were also calculated to quantify the relative safety and adverse effects of mCM11. According to the results, mCM11 has a high inhibitory and lethal effect on A. baumannii strains due to its cationic properties and new specific sequence. Molecular docking revealed the release of a significant amount of energy when mCM11 binds to the surface of A. baumannii in an appropriate site. The findings indicated that mCM11 IC50 (4μg/mL) lysed 2.78% of RBCs; moreover, 8 strains of Acinetobacter baumannii showed a favorable therapeutic index. The mCM11 exhibits strong antibacterial and antibiofilm activities against A. baumannii strains, suggesting its potential therapeutic role in infections caused by these strains. Similar to its impact on A. baumannii, mCM11 could be a suitable alternative to antibiotics in combat against antibiotic-resistant bacteria in the in vivo experiments.

Quercetin: Synergistic Interaction with Antibiotics against Colistin-Resistant Acinetobacter baumannii.

Infections caused by resistant strains of Acinetobacter baumannii are now a global problem that requires the immediate development of new antimicrobial drugs. Combination therapy is one of the strategies used to solve this problem. Based on this information, the purpose of this study was to determine whether quercetin (QUE), in combination with three antibiotics, is effective against colistin-resistant A. baumannii strains (ColR-Ab). The effects of the combination of QUE with colistin (COL), amikacin (AMK), and meropenem (MEM) were evaluated according to the checkerboard synergy test. The combinations of QUE + COL and QUE + AMK showed synergistic activity on ColR-Ab strains with FICI values in the range of 0.1875-0.5 and 0.1875-0.2825, respectively. A 4- to 16-fold decrease in COL MIC and a 16- to 64-fold decrease in AMK MIC values were detected. Synergistic activity was confirmed by the time-kill test, and these combinations were found to be bactericidal at the end of 24 h. According to spectrophotometric measurements, the combinations of QUE + COL and QUE + AMK induced membrane damage, leading to the leakage of nucleic acids. Cell lysis and cell death were confirmed with SEM observations. The detected synergy offers an opportunity for the future development of treatment strategies for potential infections caused by ColR-Ab strains.

Green Biofabrication of Silver Nanoparticles of Potential Synergistic Activity with Antibacterial and Antifungal Agents against Some Nosocomial Pathogens.

Nosocomial bacterial and fungal infections are one of the main causes of high morbidity and mortality worldwide, owing to the high prevalence of multidrug-resistant microbial strains. Hence, the study aims to synthesize, characterize, and investigate the antifungal and antibacterial activity of silver nanoparticles (AgNPs) fabricated using Camellia sinensis leaves against nosocomial pathogens. The biogenic AgNPs revealed a small particle diameter of 35.761 ± 3.18 nm based on transmission electron microscope (TEM) graphs and a negative surface charge of -14.1 mV, revealing the repulsive forces between nanoparticles, which in turn indicated their colloidal stability. The disk diffusion assay confirmed that Escherichia coli was the most susceptible bacterial strain to the biogenic AgNPs (200 g/disk), while the lowest sensitive strain was found to be the Acinetobacter baumannii strain with relative inhibition zones of 36.14 ± 0.67 and 21.04 ± 0.19 mm, respectively. On the other hand, the biogenic AgNPs (200 µg/disk) exposed antifungal efficacy against Candida albicans strain with a relative inhibition zone of 18.16 ± 0.14 mm in diameter. The biogenic AgNPs exposed synergistic activity with both tigecycline and clotrimazole against A. baumannii and C. albicans, respectively. In conclusion, the biogenic AgNPs demonstrated distinct physicochemical properties and potential synergistic bioactivity with tigecycline, linezolid, and clotrimazole against gram-negative, gram-positive, and fungal strains, respectively. This is paving the way for the development of effective antimicrobial combinations for the effective management of nosocomial pathogens in intensive care units (ICUs) and health care settings.