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Antibiotics (Basel, Switzerland) Jun 2024Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics....
Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [RW] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [RW] against () and methicillin-resistant (MRSA) by a checkered board assay. [RW] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [RW] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [RW] at a 16 mg/mL concentration stabilized the zeta potential of MRSA -31 ± 0.88 mV to -8.37 mV. Also, [RW] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [RW] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [RW] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [RW] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [RW] and a change in antibacterial effectiveness MIC [RW] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [RW] warrants further consideration as a potential AMP.
PubMed: 38927221
DOI: 10.3390/antibiotics13060555 -
Antibiotics (Basel, Switzerland) Jun 2024The -independent oxacillin non-susceptible (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure....
Genetic and Phenotypic Changes Related to the Development of -Independent Oxacillin Non-Susceptibility in ST8 Recovered after Antibiotic Therapy in a Patient with Bacteremia.
The -independent oxacillin non-susceptible (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA- isolates recovered during the course of antibiotic treatment from a patient suffering successive episodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked genes, and had reduced susceptibility to teicoplanin. SA2 showed higher β-lactamase activity than SAMS1. However, β-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (, , , , and /), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbiologists in the region, as MIONSA detection and treatment represent an important clinical challenge.
PubMed: 38927220
DOI: 10.3390/antibiotics13060554 -
Antibiotics (Basel, Switzerland) Jun 2024, commonly known as bitter melon, is a fruiting plant that has been used for several diseases including infectious diseases. In this study, we report the antibacterial,...
, commonly known as bitter melon, is a fruiting plant that has been used for several diseases including infectious diseases. In this study, we report the antibacterial, antifungal, and antiviral activity of different bitter melon fruit parts originating from India and Saudi Arabia. The in vitro experiments are supported by the molecular docking of karavilosides to verify their role in the bioactivity. The antimicrobial assays revealed activity against , , and . The extracts exhibited the potent inhibition of HIV-I reverse transcriptase, with an IC50 of 0.125 mg/mL observed for the pith extract originating from Saudi Arabia and the standard drug doxorubicin. The molecular docking of karavilosides exhibited a significant affinity to reverse transcriptase comparable to Rilpivirine and higher than that of doxorubicin. These outcomes encourage the precious bioactive components of the seed and pith of the Saudi bitter melon fruits to be further studied for isolation and structure elucidation.
PubMed: 38927210
DOI: 10.3390/antibiotics13060544 -
Antibiotics (Basel, Switzerland) Jun 2024The rising incidence of extensively drug-resistant (XDR) , including carbapenem- and colistin-resistant strains, leads to the limitation of available effective...
The rising incidence of extensively drug-resistant (XDR) , including carbapenem- and colistin-resistant strains, leads to the limitation of available effective antibiotics. , known as chewing tea, is produced from var. or Assam tea leaves fermentation. Previous studies revealed that the extract of contains various phenolic and flavonoid compounds with numerous biological activities including antibacterial activity. However, the antibacterial activity of against XDR bacteria especially colistin-resistant strains had not been investigated. In this study, the compositions of phenolic and flavonoid compounds in fresh, steamed, and fermented Assam tea leaves were examined by HPLC, and their antibacterial activities were evaluated by the determination of the MIC and MBC. Pyrogallol was detected only in the extract from and showed the highest activities with an MIC of 0.25 mg/mL and an MBC of 0.25-0.5 mg/mL against methicillin-susceptible , methicillin-resistant , ATCC 25922, colistin-resistant , and colistin-resistant . The effects on morphology and proteomic changes in NH54 treated with extract were characterized by SEM and label-free quantitative shotgun proteomics analysis. The results revealed that extract caused the decrease in bacterial cell wall integrity and cell lysis. The up- and downregulated expression with approximately a 2 to >5-fold change in proteins involved in peptidoglycan synthesis and outer membrane, carbohydrate, and amino acid metabolism were identified. These findings suggested that containing pyrogallol and other secondary metabolites from fermentation has potential as an alternative candidate with an antibacterial agent or natural active pharmaceutical ingredient against XDR bacteria including colistin-resistant bacteria.
PubMed: 38927202
DOI: 10.3390/antibiotics13060536 -
Antibiotics (Basel, Switzerland) May 2024Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This...
Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant (MRSA) in skin and soft tissue secretions, and the drug sensitivity of to better assist dermatologists in the diagnosis and treatment of SSSS. We reviewed the demographic characteristics, clinical manifestations, treatment regimens, therapeutic efficacy, laboratory test results, drug sensitivity, and outcome data of 79 SSSS patients from January 2012 to December 2021. Statistical analysis was performed using tests and chi-square tests. Among the 79 SSSS patients, MRSA was detected in 35 (44.3%) isolates: 34 community-acquired (CA)-MRSA (97.1%) and 1 hospital-acquired (HA)-MRSA. The SSSS incidence increased annually from 2012 to 2014 and then decreased gradually after peaking in 2015. All the isolates were sensitive to vancomycin, tigecycline, linezolid, moxifloxacin, levofloxacin, and ciprofloxacin; were completely resistant to penicillin; and had low sensitivity to clindamycin and erythromycin. Interestingly, the sensitivity of MRSA to tetracycline increased annually after 2015. The resistance rates to common drugs previously used to treat SSSS increased. These findings may accelerate diagnosis and improve empirical antibiotic use, suggesting that clinicians should prescribe drugs according to antimicrobial susceptibility.
PubMed: 38927182
DOI: 10.3390/antibiotics13060516 -
Antibiotics (Basel, Switzerland) May 2024Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial... (Review)
Review
Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial communities, comprising bacteria and fungi, exhibit resilience against antibiotics and host immune responses. Bacterial species such as , , , and commonly form biofilms on medical devices, exacerbating infection risks. Neonates and children, particularly those in intensive care units, are highly susceptible to biofilm-associated infections due to the prolonged use of invasive devices, such as central lines and endotracheal tubes. Enteral feeding tubes, crucial for neonatal nutritional support, also serve as potential sites for biofilm formation, contributing to recurrent microbial contamination. Moreover, species, including , present emerging challenges in neonatal care, with multi-drug resistant strains posing treatment complexities. Current antimicrobial therapies, while important in managing infections, often fall short in eradicating biofilms, necessitating alternative strategies. The aim of this review is to summarize current knowledge regarding antibiofilm strategies in neonates and in children. Novel approaches focusing on biofilm inhibition and dispersal show promise, including surface modifications, matrix-degrading enzymes, and quorum-sensing inhibitors. Prudent use of medical devices and exploration of innovative antibiofilm therapies are imperative in mitigating neonatal and pediatric biofilm infections.
PubMed: 38927176
DOI: 10.3390/antibiotics13060509 -
Antibiotics (Basel, Switzerland) May 2024Bacterial urinary tract infections (UTIs) occur frequently in companion animals and are often treated with antibiotics. However, antimicrobial resistance can severely...
Antimicrobial Susceptibility of Canine and Feline Urinary Tract Infection Pathogens Isolated from Animals with Clinical Signs in European Veterinary Practices during the Period 2013-2018.
Bacterial urinary tract infections (UTIs) occur frequently in companion animals and are often treated with antibiotics. However, antimicrobial resistance can severely hamper treatment success. Therefore, antimicrobial susceptibility monitoring is key. UTI isolates were obtained from dogs and cats in two collection periods (ComPath II: 2013-2014 and ComPath III: 2017-2018) as part of CEESA's ComPath programme. Susceptibility testing of the UTI isolates (2021 in total) was carried out at one central laboratory using agar and broth dilution methodology as recommended by the Clinical and Laboratory Standards Institute. was the most frequently isolated bacterium in UTI in both dogs (46.9%, 43.1%) and cats (61.2%, 48.3%) across ComPath II and ComPath III, respectively. The percentage of resistance in was low (<10%) across both programmes in both dogs and cats except for trimethoprim-sulfamethoxazole (dogs ComPath III: 12.9%; cats ComPath II: 13.0%) and enrofloxacin (10.5%), marbofloxacin (11.4%), and doxycycline (98.8%) for dogs in ComPath III. Three (7.5%) of the 40 isolated bacteria in total were MRSA and harboured . The level of multidrug resistance (MDR) was generally low and ranged from 0.0% for feline coagulase-negative spp. to 11.7% for canine spp., except for a peak of MDR observed in canine isolates from ComPath II (36.7%). Overall, antimicrobial resistance for most canine and feline UTI pathogens isolated during the ComPath II and ComPath III programmes was low (1-10%) to moderate (10-20%).
PubMed: 38927167
DOI: 10.3390/antibiotics13060500 -
Antibiotics (Basel, Switzerland) May 2024(immortelle) essential oil is one of the most popular essential oils worldwide and it has many beneficial properties, including antimicrobial. However, in this plant,...
(immortelle) essential oil is one of the most popular essential oils worldwide and it has many beneficial properties, including antimicrobial. However, in this plant, the chemical diversity of the essential oil is very pronounced. The aim of this work was to process the GC-MS results of four samples of essential oil of Serbian origin by chemometric tools, and evaluate the antimicrobial activity in vitro and in silico. Overall, 47 compounds were identified, the most abundant were -curcumene, -pinene, and -curcumene, followed by -ylangene, neryl acetate, -caryophyllene, italicene, -selinene, limonene, and italidiones. Although the four samples of essential oil used in this study were obtained from different producers in Serbia, they belong to the type of essential oil rich in sesquiterpenes (-curcumene and -curcumene chemotype). In vitro antimicrobial potential showed that five were sensitive among ten strains of tested microorganisms: , , , and . Therefore, these microorganism models were used further for in silico molecular docking through the mechanism of ATP-ase inhibitory activity. Results showed that among all compounds from essential oil, neryl acetate has the highest predicted binding energy. Artificial neural network modeling (ANN) showed that two major compounds -curcumene and -pinene, as well as minor compounds such as --ocimene, terpinolene, terpinene-4-ol, isoitalicene, italicene, --bergamotene, --bergamotene, italidiones, --farnesene, -selinene, -selinene, -selinene, and guaiol are responsible for the antimicrobial activity of essential oil. The results of this study indicate that essential oil samples rich in -curcumene, -pinene, and -curcumene cultivated in Serbia (Balkan) have antimicrobial potential both in vitro and in silico. In addition, according to ANN modeling, the proportion of neryl acetate and other compounds detected in these samples has the potential to exhibit antimicrobial activity.
PubMed: 38927166
DOI: 10.3390/antibiotics13060499 -
Antibiotics (Basel, Switzerland) May 2024It is crucial to discover novel antimicrobial drugs to combat resistance. This study investigated the antibacterial properties of halicin (SU3327), an AI-identified...
It is crucial to discover novel antimicrobial drugs to combat resistance. This study investigated the antibacterial properties of halicin (SU3327), an AI-identified anti-diabetic drug, against 13 kinds of common clinical pathogens of animal origin, including multidrug-resistant strains. Employing minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assessments, halicin demonstrated a broad-spectrum antibacterial effect. Time-killing assays revealed its concentration-dependent bactericidal activity against ATCC 25922 ( ATCC 25922), ATCC 29213 ( ATCC 29213), and S6 ( S6) after 4 h of treatment at concentrations above the MIC. Halicin exhibited longer post-antibiotic effects (PAEs) and sub-MIC effects (PA-SMEs) for 25922, 29213, and S6 compared to ceftiofur and ciprofloxacin, the commonly used veterinary antimicrobial agents, indicating sustained antibacterial action. Additionally, the results of consecutive passaging experiments over 40 d at sub-inhibitory concentrations showed that bacteria exhibited difficulty in developing resistance to halicin. Toxicology studies confirmed that halicin exhibited low acute toxicity, being non-mutagenic, non-reproductive-toxic, and non-genotoxic. Blood biochemical results suggested that halicin has no significant impact on hematological parameters, liver function, and kidney function. Furthermore, halicin effectively treated respiratory infections in murine models. These results underscore the potential of halicin as a new antibacterial agent with applications against clinically relevant pathogens in veterinary medicine.
PubMed: 38927159
DOI: 10.3390/antibiotics13060492 -
Antibiotics (Basel, Switzerland) May 2024A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their...
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC value of 0.15 μM. Additionally, it exhibited significant cytotoxic properties, with an IC value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (-9.9; -70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both and , with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π-cation bond with Phe92, and a salt bridge with the polar residue Asp27.
PubMed: 38927146
DOI: 10.3390/antibiotics13060479