Current Issue : July-September Volume : 2026 Issue Number : 3 Articles : 5 Articles
The escalation of bacterial resistance to existing antibiotics represents a growing global health challenge, exacerbated by the widespread misuse of antimicrobial agents. As a result, alternative antibacterial strategies are increasingly being explored, including phage-derived lytic proteins. In this study, we report a preliminary characterisation of a novel phagederived lytic protein identified through computational screening of bacteriophage genome sequences. A putative open reading frame, designated SM07 (1383 bp), was selected from bacteriophage sequences contributed by the University of KwaZulu-Natal to a global phage repository. The gene was synthesised, sub-cloned into the pET-30b(+) vector with an N-terminal histidine tag, and recombinantly expressed in Escherichia coli BL-21(AI) cells. The protein was purified using affinity and ion-exchange chromatography. Purified SM07 exhibited in vitro antimicrobial activity against Pseudomonas aeruginosa, with a minimum inhibitory concentration of 4 μg/mL, while no significant cytotoxic effects were observed in Vero kidney cells at concentrations substantially above the effective dose. Together, these findings provide initial evidence supporting the antimicrobial potential of SM07 and highlight phage-derived lytic proteins as candidates for further investigation as alternative agents against P. aeruginosa-associated infections....
Background/Objectives: Acinetobacter baumannii is a leading cause of healthcare-associated infections and is frequently associated with multidrug resistance, severely limiting therapeutic options. The increasing prevalence of carbapenem-resistant A. baumannii (CRAB) has intensified interest in novel antimicrobial agents such as cefiderocol, eravacycline, and imipenem–relebactam. Methods: A total of 80 multidrug-resistant (MDR) A. baumannii isolates recovered from various clinical specimens between April 2019 and October 2023 were included. Antimicrobial susceptibility testing was performed using disk diffusion, gradient test, and broth microdilution methods in accordance with EUCAST and CLSI recommendations. The minimum inhibitory concentrations (MIC’s) for cefiderocol were evaluated with broth microdilution using iron-depleted cation-adjusted Mueller–Hinton broth as the reference method. The presence of carbapenem resistance–associated genes (blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaIMP, and tetA) was investigated by polymerase chain reaction. Results: All isolates were resistant to imipenem and meropenem. Colistin resistance was detected in 7.5% of isolates. According to EUCAST criteria, cefiderocol susceptibility was observed in 77.5% of isolates by microdilution and in 81.25% by disk diffusion. Eravacycline demonstrated low MIC values, with MIC50 and MIC90 of 0.25 mg/L and 0.75 mg/L, respectively. In contrast, all isolates were resistant to imipenem–relebactam. The blaOXA-23 gene was detected in 82.5% and blaOXA-24 in 17.5% of isolates, while no blaOXA-58, blaIMP, or tetA genes were identified. No statistically significant association was found between cefiderocol resistance and OXA-type carbapenemase genes. Conclusions: Cefiderocol and eravacycline demonstrated promising in vitro activity against MDR A. baumannii, including colistin-resistant isolates, whereas imipenem–relebactam showed no activity. These findings support the potential role of cefiderocol and eravacycline as alternative treatment options for CRAB infections and highlight the multifactorial nature of cefiderocol resistance beyond OXA-type carbapenemase production....
Background: The increasing antimicrobial resistance has led to a greater demand for alternative treatment options, which in turn has increased interest in naturally occurring biomolecules such as pyocyanin. Methods: In this study, a three-factor Box–Behnken Design (BBD)-based response surface methodology (RSM) was employed to optimize the effects of glycerol, peptone, and pH on pyocyanin production by Pseudomonas aeruginosa OG1. The antimicrobial efficacy of the optimized pyocyanin was subsequently evaluated in vitro against three Candida species and four clinically important bacterial pathogens using the disk diffusion method, with gentamicin and fluconazole used as positive controls. Results: The second-order polynomial model demonstrated excellent fit (F = 176.3, p < 0.0001) with a non-significant lack of fit, indicating adequate representation of the experimental data. The optimal conditions were determined to be glycerol at 1.11% (w/v), peptone at 17.86 g/L, and a pH of 7.27, yielding a predicted pyocyanin concentration of 25.92 mg/L. Antimicrobial testing revealed broad-spectrum, dose-dependent activity against all tested microorganisms. The highest efficacy was observed against Bacillus cereus (26.4 ± 1.3 mm at 40 μg/mL), followed by Candida glabrata (21.5 ± 1.6 mm), Klebsiella pneumoniae (17.6 ± 1.4 mm), Candida albicans (15.4 ± 1.8 mm), Candida parapsilosis (13.2 ± 1.9 mm), Proteus mirabilis (12.5 ± 1.3 mm), and MRSA Staphylococcus aureus (9.2 ± 1.1 mm). Conclusions: These findings demonstrate that BBD-based RSM is a robust approach for optimizing pyocyanin production and that pyocyanin represents a promising dose-dependent antimicrobial agent against susceptible pathogens....
Tebipenem is a new carbapenem antibiotic that binds to penicillin-binding proteins (PBPs). Given the need for effective antibiotics against multidrug-resistant (MDR) bacteria, this review evaluated the in vitro antimicrobial activity of tebipenem against Gram-negative and Gram-positive bacteria, focusing on uropathogens. Five resources (Google Scholar, Web of Science, Embase, Scopus, and PubMed) were used to identify relevant articles. Of the 1322 articles identified, 9 relevant studies were included, which evaluated 12,501 Gramnegative and 122 Gram-positive pathogens. All nine studies (100%) assessed the activity of tebipenem against Escherichia coli, with an MIC90 value range of 0.015–>4 mg/L. Seven studies (77.8%) included Klebsiella pneumoniae, with an MIC90 value range of 0.015–0.5 mg/L. Six studies (66.7%) reported data on Proteus mirabilis, with an MIC90 value range of ≤0.125– 0.5 mg/L. Two studies (22.2%) evaluated the activity of tebipenem against Enterococcus faecalis, with MIC90 of 1 mg/L among vancomycin-susceptible isolates and 32 mg/L in isolates with not-reported mechanisms of resistance. Two studies (22.2%) evaluated the activity of tebipenem against Enterococcus faecium, with MIC90 of >4 mg/L among both vancomycin-susceptible and vancomycin-resistant isolates and MIC90 of 128 mg/L among isolates with no resistance mechanism reported. Tebipenem demonstrated good activity against Enterobacterales, such as E. coli and K. pneumoniae. The antimicrobial agent exhibited higher MICs and a higher proportion of resistance among P. mirabilis isolates. Tebipenem could be effective for outpatient treatment of infections caused by MDR Gram-negative pathogens. However, given its potential to exert selective pressure for the development of antimicrobial resistance, it should be considered for patients with cUTIs when none of the first-line treatment options demonstrate in vitro antimicrobial activity....
Background: Enterococcus faecalis is a major cause of complicated urinary tract infections (UTIs), characterized by intrinsic resistance and pronounced biofilm formation. Nitroxoline (NTX), a metal-chelating uroantiseptic, accumulates in urine and exhibits antibiofilm activity. Hydroquinone (HQ), the active urinary metabolite of arbutin-containing herbal preparations, is also excreted into urine and may contribute to antimicrobial activity in situ. This study investigated the antimicrobial and antibiofilm effects of NTX and HQ, individually and in combination, against uropathogenic E. faecalis isolates. Methods: Minimum inhibitory (MIC), bactericidal (MBC), and anti-adhesion (MAC) concentrations were determined using broth microdilution. Interaction was assessed by the checkerboard method and expressed as the fractional inhibitory concentration index (FICI). Biofilm inhibition was quantified by colony-forming unit (CFU) enumeration following exposure to subinhibitory concentrations. Ultrastructural alterations of E. faecalis following exposure to NTX and HQ were examined by transmission electron microscopy (TEM). Results: NTX demonstrated MIC values ranging from 0.002–0.016 mg/mL (MIC50/MIC90: 0.004/0.008 mg/mL), while HQ exhibited MIC values of 0.78–1.56 mg/mL (MIC50/MIC90: 0.78/1.56 mg/mL). Synergistic interactions (FICI ≤ 0.5) were observed in selected isolates, with up to eightfold and sixteenfold reductions in NTX and HQ concentrations, respectively. Additive effects predominated in the remaining isolates without antagonism. The combination achieved 3–5 log10 reductions in adherent bacterial counts compared to untreated controls and up to 4 log10 reductions compared to single-agent exposure. In several strains, complete inhibition of adhesion was observed. TEM analysis revealed marked envelope disruption, cytoplasmic condensation, and structural collapse following combined treatment. Conclusions: Given that both NTX and HQ are active within the urinary environment, their combination may represent a pharmacologically relevant strategy targeting both bacterial growth and early biofilm establishment in enterococcal UTIs. These findings support further in vivo and pharmacokinetic investigations to evaluate the clinical applicability of this combination....
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