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International Journal of Molecular... Jun 2024bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major... (Review)
Review
bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major challenge to clinicians and have been consistently shown to increase the risk of mortality and other infectious complications. , while typically not considered an intracellular pathogen, has been proven to utilize an intracellular niche, through several phenotypes including small colony variants, as a means for survival that has been linked to chronic, persistent, and recurrent infections. This intracellular persistence allows for protection from the host immune system and leads to reduced antibiotic efficacy through a variety of mechanisms. These include antimicrobial resistance, tolerance, and/or persistence in that contribute to persistent bacteremia. This review will discuss the challenges associated with treating these complicated infections and the various methods that uses to persist within the intracellular space.
Topics: Bacteremia; Humans; Staphylococcus aureus; Staphylococcal Infections; Anti-Bacterial Agents; Animals; Drug Resistance, Bacterial
PubMed: 38928191
DOI: 10.3390/ijms25126486 -
Biomedicines Jun 2024Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body's own innate bactericidal mechanisms. It also provides...
Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body's own innate bactericidal mechanisms. It also provides anti-adhesive effects against both Streptococcus pneumoniae and Haemophilus influenza. This study was performed to evaluate the efficacy and safety of xylitol nasal irrigation in the postoperative care of functional endoscopic sinus surgery (FESS). Patients with chronic rhinosinusitis who received FESS were recruited and randomly assigned to two groups at one month post-surgery. Thirty-five patients in the xylitol group received 400 mL of 5% xylitol nasal irrigation daily for 2 months, while another 35 in the normal saline (NS) group received 400 mL of NS nasal irrigation daily for 2 months. Prior to FESS, as well as before and after nasal irrigation, sinonasal symptoms were assessed through the 22-item Sino-Nasal Outcome Test Questionnaire. The patients also underwent an endoscopic examination while undergoing nasal function tests, and a cytokine measurement of the nasal lavage and a bacterial culture from the middle meatus were performed. The safety of the nasal irrigation was assessed through any self-reported adverse events, the Eustachian Tube Dysfunction Patient Questionnaire and the eustachian tube function test. The endoscopic scores and olfactory threshold significantly decreased after xylitol irrigation when compared with those before irrigation. The prevalence of Staphylococcus aureus in the nasal secretions also decreased significantly after xylitol irrigation. The amounts of Interleukin-5 and Interleukin-17A were significantly increased in the nasal lavage after xylitol irrigation. No side effects, including those related to eustachian tube function, were seen after nasal irrigation in both groups. Our results showed that xylitol nasal irrigation was both beneficial and safe during the postoperative care of FESS.
PubMed: 38927584
DOI: 10.3390/biomedicines12061377 -
Biology May 2024Mammary gland bioreactors are promising methods for recombinant protein production. Human neutrophil peptide 1 (HNP1) exhibits antibacterial and immune-modulating...
Mammary gland bioreactors are promising methods for recombinant protein production. Human neutrophil peptide 1 (HNP1) exhibits antibacterial and immune-modulating properties. This study aims to establish a method to generate goats secreting HNP1 using the mammary gland as bioreactors. HNP1 transgenic goats were generated by using CRISPR/Cas9 technology to knock-in (KI) the HNP1 sequence into exon 7 of the goat β-casein (CSN2) gene under the control of the CSN2 promoter. One-cell stage embryos were cytoplasmically injected with a mixture of Cas9 mRNA, sgRNA, and a homologous plasmid including the T2A-HNP1 sequences, followed by transfer to recipient goats. A total of 22 live offspring goats were delivered, and 21 of these goats (95.45%) exhibited targeted edits at the locus, and 2 female goats (9.09%) demonstrated successful HNP1 integration. Western blot and ELISA analyses confirmed the presence of HNP1 protein at high levels in the milk of these HNP1-positive goats, with mean concentrations of 22.10 µg/mL and 0.0092 µg/mL during the initial 60 days of lactation. Furthermore, milk from these transgenic goats exhibited notable antibacterial activity against Escherichia coli and Staphylococcus aureus, demonstrating the functionality of the expressed HNP1 protein. In conclusion, we established an efficient method for developing new transgenic goat lines as a mammary gland bioreactor, and the bioactive HNP1 protein secreted by the transgenic goat has the potential to combat microbial resistance.
PubMed: 38927247
DOI: 10.3390/biology13060367 -
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