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Frontiers in Bioscience (Landmark... Apr 2024The antibiotic resistance of microorganisms is escalating rapidly. Infections caused by opportunistic pathogens in immunocompromised individuals have prompted...
BACKGROUND
The antibiotic resistance of microorganisms is escalating rapidly. Infections caused by opportunistic pathogens in immunocompromised individuals have prompted researchers to seek for potent and safe antibacterial agents. The purpose of this investigation was to explore the suppression of virulence gene expression, specifically the operon genes responsible in biofilm formation in , through the utilization of metabolites obtained from probiotic bacteria.
METHODS
To assess the antimicrobial properties, standard strains of five probiotic bacteria were tested against a standard strain of multidrug-resistant (MDR) employing the agar gel diffusion technique. Following the identification of the most potent probiotic strain (), the existence of its and genes was confirmed using the polymerase chain reaction (PCR) test. High-performance liquid chromatography (HPLC) and fourier-transform infrared spectroscopy (FTIR) techniques were employed to identify the intended metabolite, which was found to be a lipopeptide nature. The minimum inhibitory concentration (MIC) values and anti-biofilm activity of the targeted metabolite were determined using a dilution method in 96-well microplates and field emission scanning electron microscopy (FE-SEM). Real-time PCR (qPCR) was utilized for comparing the expression of operon genes, including , in pre- and post-exposure to the derived lipopeptide.
RESULTS
The MIC results indicated that the probiotic product inhibited the growth of at concentrations lower than those needed for conventional antibiotics. Furthermore, it was observed that the desired genes' expression decreased due to the effect of this substance.
CONCLUSIONS
This research concludes that the probiotic product could be a viable alternative for combating drug resistance in .
Topics: Acinetobacter baumannii; Probiotics; Anti-Bacterial Agents; Microbial Sensitivity Tests; Biofilms; Lipopeptides; Bacillus licheniformis; Drug Resistance, Multiple, Bacterial
PubMed: 38812307
DOI: 10.31083/j.fbl2905171 -
Frontiers in Cellular and Infection... 2024Among the genus, stands out as an important opportunistic infection causative agent commonly found in hospital settings, which poses a serious threat to human health....
Among the genus, stands out as an important opportunistic infection causative agent commonly found in hospital settings, which poses a serious threat to human health. Recently, the high prevalence of carbapenem-resistant isolates has created significant therapeutic challenges for clinicians. Bacteriophages and their derived enzymes are promising therapeutic alternatives or adjuncts to antibiotics effective against multidrug-resistant bacterial infections. However, studies investigating the depolymerases specific to strains are scarce. In this study, we identified and characterized a capsule depolymerase, Dpo27, encoded by the bacteriophage IME-Ap7, which targets . A total of 23 clinical isolates of spp. were identified as (21.91%, 23/105), and seven strains with various K locus (KL) types (KL14, KL32, KL38, KL111, KL163, KL207, and KL220) were used as host bacteria for phage screening. The lytic phage IME-Ap7 was isolated using 7 (KL220) as an indicator bacterium and was observed for depolymerase activity. A putative tail fiber gene encoding a polysaccharide-degrading enzyme (Dpo27) was identified and expressed. The results of the modified single-spot assay showed that both 7 and 1492 were sensitive to Dpo27, which was assigned the KL220 type. After incubation with Dpo27, strain was susceptible to killing by human serum; moreover, the protein displayed no hemolytic activity against erythrocytes. Furthermore, the protein exhibited sustained activity across a wide pH range (5.0-10.0) and at temperatures between 20 and 50°C. In summary, the identified capsule depolymerase Dpo27 holds promise as an alternative treatment for combating KL220-type infections.
Topics: Bacteriophages; Humans; Acinetobacter; Acinetobacter Infections; Glycoside Hydrolases; Bacterial Capsules
PubMed: 38808067
DOI: 10.3389/fcimb.2024.1373052 -
Viruses May 2024The genus comprises both environmental and clinically relevant species associated with hospital-acquired infections. Among them, is a critical priority bacterial...
The genus comprises both environmental and clinically relevant species associated with hospital-acquired infections. Among them, is a critical priority bacterial pathogen, for which the research and development of new strategies for antimicrobial treatment are urgently needed. spp. produce a variety of structurally diverse capsular polysaccharides (CPSs), which surround the bacterial cells with a thick protective layer. These surface structures are primary receptors for capsule-specific bacteriophages, that is, phages carrying tailspikes with CPS-depolymerizing/modifying activities. Phage tailspike proteins (TSPs) exhibit hydrolase, lyase, or esterase activities toward the corresponding CPSs of a certain structure. In this study, the data on all lytic capsule-specific phages infecting spp. with genomes deposited in the NCBI GenBank database by January 2024 were summarized. Among the 149 identified TSPs encoded in the genomes of 143 phages, the capsular specificity (K specificity) of 46 proteins has been experimentally determined or predicted previously. The specificity of 63 TSPs toward CPSs, produced by various K types, was predicted in this study using a bioinformatic analysis. A comprehensive phylogenetic analysis confirmed the prediction and revealed the possibility of the genetic exchange of gene regions corresponding to the CPS-recognizing/degrading parts of different TSPs between morphologically and taxonomically distant groups of capsule-specific phages.
Topics: Bacteriophages; Acinetobacter; Bacterial Capsules; Phylogeny; Genome, Viral; Viral Tail Proteins; Polysaccharides; Polysaccharides, Bacterial; Acinetobacter baumannii; Glycoside Hydrolases
PubMed: 38793652
DOI: 10.3390/v16050771 -
Viruses May 2024has developed multiple drug resistances, posing a significant threat to antibiotic efficacy. LysECD7, an endolysin derived from phages, could be a promising therapeutic...
has developed multiple drug resistances, posing a significant threat to antibiotic efficacy. LysECD7, an endolysin derived from phages, could be a promising therapeutic agent against multi-drug resistance . In this study, in order to further enhance the antibacterial efficiency of the engineered LysECD7, a few lipopolysaccharide-interacting peptides (Li5, MSI594 and Li5-MSI) were genetically fused with LysECD7. Based on in vitro antibacterial activity, the fusion protein Lys-Li5-MSI was selected for further modifications aimed at extending its half-life. A cysteine residue was introduced into Lys-Li5-MSI through mutation (Lys-Li5-MSI), followed by conjugation with a C16 fatty acid chain via a protonation substitution reaction(V12C-C16). The pharmacokinetic profile of V12C-C16 exhibited a more favorable characteristic in comparison to Lys-Li5-MSI, thereby resulting in enhanced therapeutic efficacy against lethal infection in mice. The study provides valuable insights for the development of novel endolysin therapeutics and proposes an alternative therapeutic strategy for combating infections.
Topics: Acinetobacter baumannii; Animals; Endopeptidases; Mice; Acinetobacter Infections; Anti-Bacterial Agents; Lipopolysaccharides; Fatty Acids; Microbial Sensitivity Tests; Peptides; Recombinant Fusion Proteins; Female; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 38793641
DOI: 10.3390/v16050760 -
Viruses May 2024Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may...
Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to assess the costs of phage resistance on the virulence of priority 1 nosocomial pathogenic bacterium, . By subjecting phage-resistant variant Ev5-WHG of WHG40004 to several virulence profiles, we found that its resistance to phage is associated with reduced fitness in host microenvironments. Also, the mutant exhibited impaired adhesion and invasion to mammalian cells, as well as increased susceptibility to macrophage phagocytosis. Furthermore, the whole-genome sequencing of the mutant revealed that there exist multiple mutations which may play a role in phage resistance and altered virulence. Altogether, this study demonstrates that resistance to phage can significantly alter phenotypes associated with virulence in .
Topics: Acinetobacter baumannii; Virulence; Bacteriophages; Phenotype; Acinetobacter Infections; Animals; Humans; Macrophages; Mutation; Phagocytosis; Whole Genome Sequencing; Mice
PubMed: 38793624
DOI: 10.3390/v16050743 -
Frontiers in Public Health 2024This study aimed to explore the risk factors for failed treatment of carbapenem-resistant ventilator-associated pneumonia (CRAB-VAP) with tigecycline and to establish a...
BACKGROUND
This study aimed to explore the risk factors for failed treatment of carbapenem-resistant ventilator-associated pneumonia (CRAB-VAP) with tigecycline and to establish a predictive model to predict the incidence of failed treatment and the prognosis of CRAB-VAP.
METHODS
A total of 189 CRAB-VAP patients were included in the safety analysis set from two Grade 3 A national-level hospitals between 1 January 2022 and 31 December 2022. The risk factors for failed treatment with CRAB-VAP were identified using univariate analysis, multivariate logistic analysis, and an independent nomogram to show the results.
RESULTS
Of the 189 patients, 106 (56.1%) patients were in the successful treatment group, and 83 (43.9%) patients were in the failed treatment group. The multivariate logistic model analysis showed that age (OR = 1.04, 95% CI: 1.02, 1.07, = 0.001), yes. of hypoproteinemia (OR = 2.43, 95% CI: 1.20, 4.90, = 0.013), the daily dose of 200 mg (OR = 2.31, 95% CI: 1.07, 5.00, = 0.034), yes. of medication within 14 days prior to surgical intervention (OR = 2.98, 95% CI: 1.19, 7.44, = 0.019), and no. of microbial clearance (OR = 0.31, 95% CI: 0.14, 0.70, = 0.005) were risk factors for the failure of tigecycline treatment. Receiver operating characteristic (ROC) analysis showed that the AUC area of the prediction model was 0.745 (0.675-0.815), and the decision curve analysis (DCA) showed that the model was effective in clinical practice.
CONCLUSION
Age, hypoproteinemia, daily dose, medication within 14 days prior to surgical intervention, and microbial clearance are all significant risk factors for failed treatment with CRAB-VAP, with the nomogram model indicating that high age was the most important factor. Because the failure rate of CRAB-VAP treatment with tigecycline was high, this prediction model can help doctors correct or avoid risk factors during clinical treatment.
Topics: Humans; Acinetobacter baumannii; Risk Factors; Male; Female; Middle Aged; Carbapenems; Pneumonia, Ventilator-Associated; Anti-Bacterial Agents; Aged; Logistic Models; Acinetobacter Infections; Treatment Failure; Tigecycline; Adult; Retrospective Studies; China; Drug Resistance, Bacterial
PubMed: 38784576
DOI: 10.3389/fpubh.2024.1385118 -
International Journal For Parasitology.... Aug 2024Ticks are obligate hematophagous ectoparasites of vertebrates and are relevant worldwide due to the number of bacterial and other pathogens they can transmit. To date,...
Ticks are obligate hematophagous ectoparasites of vertebrates and are relevant worldwide due to the number of bacterial and other pathogens they can transmit. To date, the knowledge about the microorganisms that ticks harbor and transmit to their hosts is incipient. In this study, 24 samples of mammals belonging to four taxonomic orders and ticks of the genera and from the Orinoco region of Colombia were analyzed to described and compare the bacterial microbiome. Genetic extraction was performed, and the V3-V4 region of the rRNA gene was amplified by PCR. Libraries were created, and those samples with adequate quality indices were sequenced using Illumina MiSeq technology. Bacterial taxonomic assignment analyses were conducted through Amplicon Sequence Variants (ASVs) and Operational Taxonomic Units (OTUs). The results correspond to 16 samples that passed the quality filters, with 3218 OTUs (415 families). Although a considerable number of unknown bacteria was found, Enterobacteriaceae, Beijerinckiaceae, Moraxellaceae, and Burkholderiaceae are the most prevalent families, and the presence of the genera , , , which can harbor pathogenic species was confirmed. In individuals of found actively feeding on , bacteria of the genera and were documented. Similarly, found actively feeding on shared . was shared among the blood samples of , while and were shared in blood and liver samples of . Shared bacteria between and included , , and . The results highlight the need of additional studies in other natural regions of Colombia and other American countries where tick-borne diseases have been detected. Likewise, the recorded data are the first at the level of bacterial communities in ticks of the family Ixodidae and provide valuable knowledge for the understanding host-tick and pathogen interactions.
PubMed: 38778917
DOI: 10.1016/j.ijppaw.2024.100943 -
Journal of Nanobiotechnology May 2024The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development.
BACKGROUND
The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development.
RESULTS
A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20-40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model.
CONCLUSIONS
The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development.
Topics: Acinetobacter baumannii; Animals; Acinetobacter Infections; Mice; Bacteriophages; Female; Mice, Inbred BALB C; Bacterial Vaccines; Immunization; Extracellular Vesicles; Bacterial Outer Membrane; Bacterial Outer Membrane Proteins; Disease Models, Animal; Humans; Administration, Intranasal; Viral Proteins
PubMed: 38773507
DOI: 10.1186/s12951-024-02553-x -
Antimicrobial Resistance and Infection... May 2024Currently, different guidelines recommend using different methods to determine whether deduplication is necessary when determining the detection rates of...
Implications of deduplication on the detection rates of multidrug-resistant organism (MDRO) in various specimens: insights from the hospital infection surveillance program.
BACKGROUND
Currently, different guidelines recommend using different methods to determine whether deduplication is necessary when determining the detection rates of multidrug-resistant organisms (MDROs). However, few studies have investigated the effect of deduplication on MDRO monitoring data. In this study, we aimed to investigate the influence of deduplication on the detection rates of MDROs in different specimens to assess its impact on infection surveillance outcomes.
METHODS
Samples were collected from hospitalized patients admitted between January 2022 and December 2022; four types of specimens were collected from key monitored MDROs, including sputum samples, urine samples, blood samples, and bronchoalveolar lavage fluid (BALF) samples. In this study, we compared and analysed the detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Escherichia coli (CRECO), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA) under two conditions: with and without deduplication.
RESULTS
When all specimens were included, the detection rates of CRKP, CRAB, CRPA, and MRSA without deduplication (33.52%, 77.24%, 44.56%, and 56.58%, respectively) were significantly greater than those with deduplication (24.78%, 66.25%, 36.24%, and 50.83%, respectively) (all P < 0.05). The detection rates in sputum samples were significantly different between samples without duplication (28.39%, 76.19%, 46.95%, and 70.43%) and those with deduplication (19.99%, 63.00%, 38.05%, and 64.50%) (all P < 0.05). When deduplication was not performed, the rate of detection of CRKP in urine samples reached 30.05%, surpassing the rate observed with deduplication (21.56%) (P < 0.05). In BALF specimens, the detection rates of CRKP and CRPA without deduplication (39.78% and 53.23%, respectively) were greater than those with deduplication (31.62% and 42.20%, respectively) (P < 0.05). In blood samples, deduplication did not have a significant impact on the detection rates of MDROs.
CONCLUSION
Deduplication had a significant effect on the detection rates of MDROs in sputum, urine, and BALF samples. Based on these data, we call for the Infection Prevention and Control Organization to align its analysis rules with those of the Bacterial Resistance Surveillance Organization when monitoring MDRO detection rates.
Topics: Humans; Drug Resistance, Multiple, Bacterial; Cross Infection; Klebsiella pneumoniae; Sputum; Methicillin-Resistant Staphylococcus aureus; Acinetobacter baumannii; Anti-Bacterial Agents; Pseudomonas aeruginosa; Bronchoalveolar Lavage Fluid; Carbapenems; Escherichia coli; Epidemiological Monitoring; Hospitals
PubMed: 38769515
DOI: 10.1186/s13756-024-01408-2 -
BMC Veterinary Research May 2024Acinetobacter lwoffii (A.lwoffii) is a serious zoonotic pathogen that has been identified as a cause of infections such as meningitis, bacteremia and pneumonia. In...
BACKGROUND
Acinetobacter lwoffii (A.lwoffii) is a serious zoonotic pathogen that has been identified as a cause of infections such as meningitis, bacteremia and pneumonia. In recent years, the infection rate and detection rate of A.lwoffii is increasing, especially in the breeding industry. Due to the presence of biofilms, it is difficult to eradicate and has become a potential super drug-resistant bacteria. Therefore, eradication of preformed biofilm is an alternative therapeutic action to control A.lwoffii infection. The present study aimed to clarify that baicalin could eradicate A.lwoffii biofilm in dairy cows, and to explore the mechanism of baicalin eradicating A.lwoffii.
RESULTS
The results showed that compared to the control group, the 4 MIC of baicalin significantly eradicated the preformed biofilm, and the effect was stable at this concentration, the number of viable bacteria in the biofilm was decreased by 0.67 LogCFU/mL. The total fluorescence intensity of biofilm bacteria decreased significantly, with a reduction rate of 67.0%. There were 833 differentially expressed genes (367 up-regulated and 466 down-regulated), whose functions mainly focused on oxidative phosphorylation, biofilm regulation system and trehalose synthesis. Molecular docking analysis predicted 11 groups of target proteins that were well combined with baicalin, and the content of trehalose decreased significantly after the biofilm of A.lwoffii was treated with baicalin.
CONCLUSIONS
The present study evaluated the antibiofilm potential of baicalin against A.lwoffii. Baicalin revealed strong antibiofilm potential against A.lwoffii. Baicalin induced biofilm eradication may be related to oxidative phosphorylation and TCSs. Moreover, the decrease of trehalose content may be related to biofilm eradication.
Topics: Biofilms; Animals; Flavonoids; Acinetobacter; Cattle; Milk; Anti-Bacterial Agents; Microbial Sensitivity Tests; Molecular Docking Simulation; Female; Acinetobacter Infections
PubMed: 38764041
DOI: 10.1186/s12917-024-04015-w