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International Journal of Molecular... May 2024The escalating threat of multidrug-resistant pathogens necessitates innovative approaches to combat infectious diseases. In this study, we examined peptides R23F*,...
The escalating threat of multidrug-resistant pathogens necessitates innovative approaches to combat infectious diseases. In this study, we examined peptides R23F*, V31K*, and R44K*, which were engineered to include an amyloidogenic fragment sourced from the S1 protein of , along with one or two cell-penetrating peptide (CPP) components. We assessed the antimicrobial efficacy of these peptides in a liquid medium against various strains of both Gram-positive bacteria, including (209P and 129B strains), MRSA (SA 180 and ATCC 43300 strains), and (strain IP 5832), and Gram-negative bacteria such as (ATCC 28753 and 2943 strains) and (MG1655 and K12 strains). Peptides R23F*, V31K*, and R44K* exhibited antimicrobial activity comparable to gentamicin and meropenem against all tested bacteria at concentrations ranging from 24 to 48 μM. The peptides showed a stronger antimicrobial effect against . Notably, peptide R44K* displayed high efficacy compared to peptides R23F* and V31K*, particularly evident at lower concentrations, resulting in significant inhibition of bacterial growth. Furthermore, modified peptides V31K* and R44K* demonstrated enhanced inhibitory effects on bacterial growth across different strains compared to their unmodified counterparts V31K and R44K. These results highlight the potential of integrating cell-penetrating peptides, amyloidogenic fragments, and amino acid residue modifications to advance the innovation in the field of antimicrobial peptides, thereby increasing their effectiveness against a broad spectrum of pathogens.
Topics: Cell-Penetrating Peptides; Antimicrobial Peptides; Microbial Sensitivity Tests; Anti-Bacterial Agents; Amino Acids; Drug Design; Amyloidogenic Proteins
PubMed: 38892216
DOI: 10.3390/ijms25116030 -
Microbiology Spectrum Jun 2024The management of infections caused by multiresistant bacteria has become of fundamental importance for any medical practice. Glycine is the most common and the simplest...
The management of infections caused by multiresistant bacteria has become of fundamental importance for any medical practice. Glycine is the most common and the simplest non-essential amino acid in humans. Glycine is very effective in improving health and supporting growth and wellbeing of humans and animals. Instead, for many bacteria, high concentrations of glycine induce lysis or deep morphological alterations. The effect of glycine on multidrug resistant (MDR) microorganisms has not yet been extensively researched. The present study was conducted 1) to establish the effect of glycine on different nosocomial pathogens isolated during routine diagnostic investigations; 2) to determine the minimum inhibitory concentration of glycine and the type of activity performed (bacteriostatic or bactericidal) on representative isolates; 3) to test the interaction between glycine and meropenem, cefiderocol, or colistin. The data reported here show a dose-dependent activity of glycine on bacteria and its bactericidal activity on MDR bacteria. Furthermore, we found that the action of glycine restores the susceptibility of multiresistant nosocomial pathogens to the tested antibiotics.IMPORTANCEAntimicrobial resistance is a constantly growing concern throughout the world, and Italy is among the Western countries where antimicrobial resistance is most widespread. In Tuscany, carbapenemase-producing are now even endemic. In this study, we challenged some resistant bacteria with a well-known molecule, glycine, the antibacterial properties of which have been known since the past century. This study could bring new insights into combining antibiotics with the simplest of all amino acids. The restoration of sensitivity to the aforementioned antibiotics by a natural compound, already used for clinical purposes, is of extreme importance in an era of proliferation of multiresistant bacteria. The use of this amino acid in evaluating its effectiveness against infections should be investigated. The low cost of this molecule can also make it easy to use even in low-income countries.
PubMed: 38888315
DOI: 10.1128/spectrum.00164-24 -
Frontiers in Cellular and Infection... 2024spp. is a genus of bacteria that is known to be closely related to . It has been debated whether should be reclassified as a subgroup of . The aim of this study is to... (Comparative Study)
Comparative Study
PURPOSE
spp. is a genus of bacteria that is known to be closely related to . It has been debated whether should be reclassified as a subgroup of . The aim of this study is to compare clinical aspects of and , a species of that is known to be bacteriologically similar to spp.
METHODS
Using data collected at a tertiary care hospital in the United States, we identified 43 patients with infection and 1173 patients with infection. We compared patient demographics (age and sex), hospitalization status, isolation sites and antibiotic resistance profiles between the two species.
RESULTS
There was no significant difference in patient demographics between the two bacteria species. The proportions of intensive care unit (ICU) admission were higher among patients with infection (p=0.008). The most common site of isolation was urine for both species (39.5% of all patients with spp. vs. 59.3% for ). The second most common site of isolation was blood stream for spp. (23.3%) and respiratory tract for (10.8%). Except for the high proportion of resistant isolates of spp. for Trimethoprim/sulfamethoxazole, the antibiotic susceptibility profiles were similar between the two bacteria species. Both were susceptible to ciprofloxacin and meropenem.
CONCLUSION
While there are no significant differences in the patient demographics and antibiotic susceptibility profiles between spp. and , may cause more serious infection requiring ICU admissions. Also, may cause blood stream infection more frequently than .
Topics: Humans; Male; Klebsiella oxytoca; Female; Middle Aged; Aged; Enterobacteriaceae; Klebsiella Infections; Anti-Bacterial Agents; Enterobacteriaceae Infections; Microbial Sensitivity Tests; Adult; Tertiary Care Centers; Intensive Care Units; United States; Aged, 80 and over; Drug Resistance, Bacterial
PubMed: 38887491
DOI: 10.3389/fcimb.2024.1260212 -
Cureus May 2024Introduction Antimicrobial resistance poses a significant global healthcare challenge in the management of bacterial infections, which is frequently attributed to rapid...
Introduction Antimicrobial resistance poses a significant global healthcare challenge in the management of bacterial infections, which is frequently attributed to rapid bacterial adaptations. This study aims to develop an antibiogram for a tertiary care hospital, providing comprehensive antibiotic sensitivity profiles for Gram-positive and Gram-negative bacteria. It informs healthcare providers of antibiotic resistance trends, enabling informed treatment decisions and enhanced infection control measures. Methods We conducted a six-month prospective observational study, during which we gathered and analyzed data from the microbiology laboratory to identify patterns of antimicrobial sensitivity. Subsequently, the data underwent analysis and interpretation using the respected WHONET software, a readily available tool designed for this specific task. Our methodology adhered to the guidelines established by the Clinical & Laboratory Standards Institute for the standardization of antibiogram generation procedures, and these guidelines are easily integrated into the WHONET software for analytical purposes. Results There were a total of 357 isolates across various hospital departments, comprising 13 distinct bacterial species. Among them, nine were identified as Gram-negative bacteria, accounting for 262 (73.3%) isolates. accounted for 131 (36.6%) isolates, while accounted for 62 (17.3%), emerging as the predominant species among them. The remaining four bacterial species were identified as Gram-positive bacteria, totaling 95 (26.6%) isolates, with being the most frequently isolated species at 51 (14.2%), followed by at 26 (7.2%). Subsequent analysis using the WHONET software facilitated the creation of an antibiogram. Among the Gram-negative bacteria, displayed high sensitivity (100%) to aztreonam and clindamycin, followed by nitrofurantoin (98%), imipenem (94%), and meropenem (95%). However, it exhibited decreased sensitivity to ampicillin (25%), cefuroxime (34%), and ceftriaxone (39%). Conversely, among the Gram-positive bacteria, demonstrated 100% sensitivity to ampicillin, amoxiclav, cefazolin, teicoplanin, linezolid, rifampicin, nitrofurantoin, and cefotaxime. However, it exhibited zero sensitivity to vancomycin and only 6% sensitivity to cotrimoxazole. Conclusion This study advances the understanding of antibiotic susceptibility in a tertiary care setting and provides an invaluable tool for optimizing treatment strategies, enhancing infection control measures, and combating antibiotic resistance.
PubMed: 38887355
DOI: 10.7759/cureus.60542 -
Annals of Clinical Microbiology and... Jun 2024Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat...
BACKGROUND
Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat pathogens due to both intrinsic resistance and the possibility of acquired antimicrobial resistance. Species identification remains challenging leading to imprecise descriptions of resistance in each taxon. Cefiderocol is a broad-spectrum siderophore cephalosporin increasingly used in the management of Achromobacter infections for which susceptibility data remain scarce. We aimed to describe the susceptibility to cefiderocol of a collection of Achromobacter strains encompassing different species and isolation sources from CF or non-CF (NCF) patients.
METHODS
We studied 230 Achromobacter strains (67 from CF, 163 from NCF patients) identified by nrdA gene-based analysis, with available susceptibility data for piperacillin-tazobactam, meropenem and trimethoprim-sulfamethoxazole. Minimal inhibitory concentrations (MICs) of cefiderocol were determined using the broth microdilution reference method according to EUCAST guidelines.
RESULTS
Strains belonged to 15 species. A. xylosoxidans represented the main species (71.3%). MICs ranged from ≤ 0.015 to 16 mg/L with MIC of ≤ 0.015/0.5 mg/L overall and 0.125/2 mg/L against 27 (11.7%) meropenem-non-susceptible strains. Cefiderocol MICs were not related to CF/NCF origin or species although A. xylosoxidans MICs were statistically lower than those of other species considered as a whole. Considering the EUCAST non-species related breakpoint (2 mg/L), 228 strains (99.1%) were susceptible to cefiderocol. The two cefiderocol-resistant strains (A. xylosoxidans from CF patients) represented 3.7% of meropenem-non-susceptible strains and 12.5% of MDR strains.
CONCLUSIONS
Cefiderocol exhibited excellent in vitro activity against a large collection of accurately identified Achromobacter strains, irrespective of species and origin.
Topics: Microbial Sensitivity Tests; Humans; Achromobacter; Anti-Bacterial Agents; Cephalosporins; Cefiderocol; Cystic Fibrosis; Gram-Negative Bacterial Infections
PubMed: 38886694
DOI: 10.1186/s12941-024-00709-z -
The Journal of Antibiotics Jun 2024Antimicrobial resistance is emerging as the new healthcare crisis necessitating the development of newer classes of drugs using non-traditional approaches. Pseudomonas...
Antimicrobial resistance is emerging as the new healthcare crisis necessitating the development of newer classes of drugs using non-traditional approaches. Pseudomonas aeruginosa, one of the most common pathogens involved in nosocomial infections, is extremely difficult to treat even with the last resort frontline drug, the carbapenems. As the pathogen has the ability to acquire resistance to new small-molecule antibiotics, being deployed, a novel biological approach has been tried using antibody fragments in combination with carbapenems and β-lactams as adjunct therapy for an enduring solution to the problem. In this study, we developed a camelid antibody fragment (VHH) library against P. aeruginosa and isolated a highly potent hit, PsC23. Mass spectrometry identified the target to be a component of the C4-dicarboxylate transporter that feeds metabolites to the glyoxylate shunt particularly under conditions of oxidative stress. PsC23 is bacteriostatic at a concentration of 1.66 µM (25 µg ml) and shows a synergistic effect with both the classes of drugs at an effective concentration of 100-200 nM (1.5-3.0 µg ml) when co administered with them. In combination with meropenem the VHH completely cleared the infection from a neutropenic mouse with a carbapenem-resistant P. aeruginosa systemic infection. Blocking the glyoxylate shunt by PsC23 resulted in disruption of energy transduction due to a respiratory shift to the oxygen-depleted TCA cycle causing inhibition of efflux and increased free radical generation from carbapenems and β-lactams exerting a strong bactericidal effect that reversed the resistance to multiple unrelated drugs.
PubMed: 38886486
DOI: 10.1038/s41429-024-00748-w -
International Journal of Systematic and... Jun 2024Strain I65 (=KACC 22647=JCM 35315), a novel Gram-stain-negative, strictly aerobic, non-motile, non-spore-forming, rod-shaped, and orange-pigmented bacterium was isolated...
Strain I65 (=KACC 22647=JCM 35315), a novel Gram-stain-negative, strictly aerobic, non-motile, non-spore-forming, rod-shaped, and orange-pigmented bacterium was isolated from influent water of a wastewater treatment system after treatment with several antibiotics, such as meropenem, gentamicin, and macrolide. The newly identified bacterial strain I65 exhibits significant multi-drug and heavy metal resistance characteristics. Strain I65 was grown in Reasoner's 2A medium [0 %-2 % (w/v) NaCl (optimum, 0 %), pH 5.0-10.0 (optimum, pH 7.0), and 20-45°C (optimum, 30 °C)]. Phylogenetic analysis based on 16S rRNA gene sequencing confirmed that strain I65 was closely related to CCBAU 05354 (99.56 % sequence similarity), THG-DN5.5 (97.51 %), and GR10-1 (97.09 %). Further analysis of the whole-genome sequence confirmed that the digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between strain I65 and CCBAU 05354 were 23.4, 80.7, and 85.0 %, respectively, suggesting that strain I65 is distinct from . The genome size of strain I65 was 6.1 Mbp, as assessed using the Oxford Nanopore platform, and its genomic DNA G+C content was 43.0 mol%. The major fatty acids of strain I65 were iso-C and iso-C G, and the major respiratory quinone was MK-7. Moreover, the major polar lipid of strain I65 was phosphatidylethanolamine. Based on genotypic, chemotaxonomic, and phenotype data, strain I65 represents a novel species belonging to the genus , for which the name sp. nov. is proposed. The type strain is I65 (=KACC 22647=JCM 35315).
Topics: Wastewater; RNA, Ribosomal, 16S; Phylogeny; DNA, Bacterial; Fatty Acids; Bacterial Typing Techniques; Base Composition; Sequence Analysis, DNA; Nucleic Acid Hybridization; Flavobacteriaceae; Anti-Bacterial Agents; Vitamin K 2; Phospholipids; Water Microbiology; Whole Genome Sequencing
PubMed: 38885037
DOI: 10.1099/ijsem.0.006425 -
JAAD Case Reports Jul 2024
Toxic epidermal necrolysis-like linear IgA bullous dermatosis as a manifestation of multiple drug hypersensitivity in the setting of drug reaction with eosinophilia and systemic symptoms.
PubMed: 38883175
DOI: 10.1016/j.jdcr.2024.04.028 -
Computational and Structural... Dec 2024Antimicrobial peptides are promising therapeutic agents for treating drug-resistant bacterial disease due to their broad-spectrum antimicrobial activity and decreased...
Antimicrobial peptides are promising therapeutic agents for treating drug-resistant bacterial disease due to their broad-spectrum antimicrobial activity and decreased susceptibility to evolutionary resistance. In this study, three novel cathelicidin antimicrobial peptides were identified from , , and by protein database mining and sequence alignment and were subsequently named TS-CATH, BM-CATH, and LV-CATH, respectively. All three peptides exhibited satisfactory antibacterial activity and broad antibacterial spectra against clinically isolated , , , and . Among them, TS-CATH displayed the best antimicrobial/bactericidal activity, with a rapid elimination efficiency against the tested drug-resistant gram-negative bacteria within 20 min, and exhibited the lowest cytotoxicity toward mammalian cells. Furthermore, TS-CATH effectively enhanced the survival rate of mice with ceftazidime-resistant bacteremia and promoted wound healing in meropenem-resistant infection. These results were achieved through the eradication of bacterial growth in target organs and wounds, further inhibiting the systemic dissemination of bacteria and the inflammatory response. TS-CATH exhibited direct antimicrobial activity by damaging the inner and outer membranes, resulting in leakage of the bacterial contents at super-MICs. Moreover, TS-CATH disrupted the bacterial respiratory chain, which inhibited ATP synthesis and induced ROS formation, significantly contributing to its antibacterial efficacy at sub-MICs. Overall, TS-CATH has potential for use as an antibacterial agent.
PubMed: 38882682
DOI: 10.1016/j.csbj.2024.05.020 -
Heliyon Jun 2024Food and waterborne outbreaks are a neglected public health problem in India. However, it is important to identify the source of infection and the causative pathogen to...
Food and waterborne outbreaks are a neglected public health problem in India. However, it is important to identify the source of infection and the causative pathogen to curb the outbreak quickly and minimize mortality and morbidity. A retrospective descriptive study was conducted with a line list of 130 diarrheal cases. Epidemiological investigation and laboratory investigation were done. Data were collected from hospital case report forms as well as interviewed affected cases. A case of acute diarrheal disease was reported among the people in the village with abdominal pain, vomiting, and diarrhea from December 31, 2022 to January 3, 2023. Out of a total of 130 recorded cases, 33 stool samples were collected and were positive for Enteroaggregative , 3a, and by cultural and molecular tests. The presumptive fecal pollution indicator assay indicated high coliform counts in the water samples (most probable number [MPN]-05) and the presence of . The identified pathogens showed susceptibility to gentamicin and meropenem. People who used public drinking water were found to be infected with acute diarrheal disease (ADD). Quick identification of the causative pathogens and their antimicrobial resistance pattern helped correct antibiotic prescriptions and quick recovery of the patients without any deaths. Thus, a timely implementation of food and waterborne outbreak investigation is crucial to saving lives and preventing the spread of infection.
PubMed: 38882280
DOI: 10.1016/j.heliyon.2024.e31903