Future microbiology最新文献

Background: The incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection following liver transplantation (LT) has been increasing. The primary objective of this study was to investigate the utility of rectal swab screening for CRKP in this patient population.

Methods: We retrospectively collected rectal swab screening data from 472 liver transplant recipients between June 2018 and December 2023. Subsequently, we analyzed the risk factors associated with CRKP bloodstream infections (BSIs) and assessed the incidence of CRKP BSIs following an intervention involving a combination therapy of tigecycline and polymyxin.

Results: Among the 472 liver transplant recipients, 38 (8.1%) tested positive for CRKP in rectal swab screening. Univariate analysis identified severe hepatitis (P = 0.008), delayed recovery of transplanted liver function (P = 0.006), and the use of anti-human thymocyte immunoglobulin (P = 0.020) as significant risk factors for CRKP BSIs. The incidence of bloodstream infection was significantly lower in recipients who received the intervention treatment compared to those who did not (P = 0.021).

Conclusions: Rectal swab screening in liver transplant recipients provides early warning for the development of CRKP BSIs. Early intervention in high-risk patients with positive rectal swab results may effectively reduce the incidence of CRKP BSIs.

Silver nanoparticles (AgNPs) have gained prominence in the scientific literature as potential antifungal therapeutic agents, especially those obtained through biological synthesis, due to their superior physicochemical properties. This review examines formulations and patents incorporating AgNPs with antifungal activity, focusing on their applicability in the treatment of mycoses, particularly in vivo. Comparative data on the mechanism of action of AgNPs in planktonic cells and biofilms are presented, as well as transcriptional analyses in fungi exposed to these nanoparticles. The results demonstrate that formulations containing AgNPs have been applied in various contexts, such as wound dressings, in combination with pharmaceuticals, dental products, and cosmetics, reflecting the growing search for therapeutic alternatives, especially for superficial infections. In experimental models, AgNPs demonstrate applicability in the treatment of dermatomycoses and opportunistic mycoses, promoting healing, low toxicity, and reducing fungal load. They can be used alone or in combination with conventional antifungals. Although still poorly understood, the impact of AgNPs on fungal gene expression suggests modulation of virulence, with potential relevant therapeutic implications. The antifungal activity of AgNPs is effective, although the required concentration varies depending on the target - planktonic cells or biofilms. These data highlight the importance of expanding studies to other fungal pathogens.

Tuberculosis, a leading killer among infectious diseases worldwide, is caused by Mycobacterium tuberculosis (Mtb). Mtb has strong ability to manipulate the intracellular environment of macrophages for successful surviving. Mitochondrion is a key organelle involved in diverse physiological processes, including Ca²⁺ fluxes, ATP synthesis, bioenergetic metabolism, and cell death, which are pivotal to cellular and organismal homeostasis. Mitochondrion is also targeted by Mtb to control various physiological responses of the host. Mtb has evolved a series of strategies to manipulate mitochondrial functions in favor of their survival, replication, and dissemination. In mitochondrion, Mtb regulates cell energy metabolism and cell death pathway. Herein, we reviewed the latest advances in the interactions between Mtb and mitochondria and discussed multiple aspects of the influence of Mtb on mitochondrial metabolism to shed light on the Mtb-induced pathogenesis.

Following the discovery of the prokaryotic adaptive immune system known as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) proteins, this technology has revolutionized biotechnology as a multifaceted genome-editing tool with a wide range of applications. CRISPR technology has not only provided novel treatment options, especially for genetic diseases, but also transformed molecular diagnostic platforms. The specific, sensitive, and adaptable nature of the CRISPR-Cas systems has led to the development of innovative solutions for the detection of diseases, including viral and bacterial infections. This review provides an overview of the CRISPR-Cas systems and mainly focuses on the application of CRISPR-based assays for the detection of Bordetella pertussis, which is the main causative agent of a highly infectious disease, whooping cough. The review emphasizes the need for novel diagnostic tools for B. pertussis, along with highlighting some future perspectives, since its diagnosis can be challenging due to nonspecific early symptoms and interference from closely related Bordetella species. In this regard, CRISPR-based diagnostic platforms can offer a promising avenue for rapid and accurate detection of B. pertussis, helping the management of whooping cough.

Streptococcus pyogenes (Group A Streptococcus) is an aerobic, gram-positive bacterium responsible for various infections such as pharyngitis, cellulitis, erysipelas, and necrotizing fasciitis. Though it rarely affects the lower respiratory tract, it can, in uncommon cases, cause community-acquired pneumonia. This study presents a rare case of rapidly progressing pneumonia caused by S. pyogenes, complicated by empyema. A 52-year-old woman presented to the emergency department with symptoms of cough, yellow sputum, night sweats, and left-sided chest pain. Initial empirical treatment with piperacillin-tazobactam was escalated to meropenem and vancomycin due to increased inflammatory markers and positive blood cultures. Blood and sputum cultures identified S. pyogenes using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Susceptibility testing confirmed sensitivity to penicillin-class antibiotics, leading to targeted therapy with ceftriaxone, ampicillin-sulbactam, and later, oral amoxicillin-clavulanate. Despite appropriate antibiotics and tube thoracostomy, no significant clinical improvement was observed. Intrapleural fibrinolytic therapy was initiated, and a favorable response was achieved through the combination of antibiotics, drainage, and fibrinolytics. The patient was ultimately discharged in good condition. In conclusion, although S. pyogenes is an uncommon cause of community-acquired pneumonia, it should be considered in cases with rapid progression and empyema complications.

Introduction: The primary purpose of this study was to estimate the global prevalence of K. pneumoniae (hvKp). isolates.

Methods: To obtain relevant data on the prevalence of hvKp strains, we searched Scopus, PubMed, Web of Science, and EMBASE. Compatible studies published in English during the last 20 years were included. We analyzed the data using a random-effects model. We assessed heterogeneity using the τ2 statistic and the DerSimonian-Laird estimator.

Results: 2427 records were gathered from 174 studies, examining 40,024 isolates to assess the hvKp prevalence. The prevalence of hvKp was 0.257 (95%CI, 0.225, 0.291). The subgroup analysis based on continents observed that the American had a minimal prevalence rate of 4.9%, whereas Africa reported a maximum rate of 27.2%. Moreover, the subgroup analysis based on countries presents the lowest rate in Mexico (1.1%) and Denmark, with the highest rate at 83.3%. No evidence of funnel plot asymmetry was detected, indicating no significant publication bias. In addition, no significant trend over time was reported.

Conclusion: This issue represents a growing clinical concern worldwide and is considered a serious alarm in treating infections caused by hvKp. Therefore, drug administration management and hospital infection control measures are strongly felt.

Biofilm is one of the causes of pathogenic bacteria's resistance to drugs. Vitamins, essential for maintaining various physiological functions within the animal body, have been observed to influence biofilm inhibition. The vitamins A, C, D, E, K, B6, and B12 possess notable anti-biofilm activity against specific pathogens, which have been reported extensively over the last few years, highlighting their potential in combating microbial infections. Vitamins B and K possess anti-quorum-sensing effects, which also contribute to the reduction of virulence factor expression of pathogenic bacteria. Many research reports have identified the incremental effectiveness of antibiotics when combined with various vitamins against bacterial infections, demonstrating a synergistic relationship between vitamins and conventional antibiotics that enhances the efficacy of antibiotics against the biofilm-mediated drug resistance capacity of microbes. According to current research, many vitamins, including vitamin A, D, and K, are responsible for binding to key proteins involved in biofilm production. However, the mechanisms of action of vitamins in combination with antibiotics against microbes require further elucidation to compensate for the existing information gap. This comprehensive review highlights, for the first time, that the least toxic biological molecules, "vitamins," can potentially manage biofilm-related microbial infections and enhance the therapeutic options available to clinicians.

Objective: To investigate the epidemiology and in vitro susceptibility of Cryptococcus neoformans to fluconazole (FLU) in HIV-negative cryptococcal meningitis (CM) patients.

Methods: Demographic and laboratory data, minimum inhibiting concentrations (MICs) of FLU, and 1-year outcomes from 270 CM patients in Guangdong Province, China, between 2011 and 2022 were retrospectively collected.

Results: 270 Cryptococcus neoformans isolates were analyzed, of which 49 (18.1%) were FLU-resistant isolates (MIC ≥8 μg/ml). The FLU MIC values and the proportion of FLU-resistant isolates showed no statistically significant temporal trend over the 12-year. However, the FLU MIC values (3.55 vs 2.84, p = 0.013) and the proportion of FLU-resistant isolates (23.9% vs 12.1%, p = 0.012) during the dry season (October to March) were higher than those during the rainy season (April to September). The 1-year mortality rates were 27.0% in the MIC ≥8 μg/ml group and 14.3% in the MIC < 8 μg/ml group. Kaplan-Meier curve showed a slight but non-significant divergence between the two groups (log-rank test p = 0.074).

Conclusions: No significant temporal trend in FLU MIC was observed. Although the majority of Cryptococcus neoformans isolates are susceptible to FLU, surveillance for emerging resistance may be warranted on a national basis.

Objectives: To investigate the antimicrobial efficacy of Melittin (MEL) against carbapenem-resistant Acinetobacter baumannii isolates as a potential alternative treatment option.

Materials and methods: Minimum Inhibitory Concentrations (MICs) of MEL, imipenem (IMP), and meropenem (MER) were evaluated through the microdilution method in 10 resistant isolates. Synergistic interactions were assessed using checkerboard, time-kill assays, and an in vivo Galleria mellonella model.

Results: MEL MICs ranged from 31.25-62.5 mg/L. Only the M5 isolate showed synergy with both combinations. Fractional Inhibitory Concentration Index (FICI) values were 0.375 for MEL+MER and 0.5 for MEL+IMP. Larvae treated with MEL combinations had increased survival rates compared to the infection group.

Conclusions: MEL appears to be a promising therapeutic candidate against carbapenem-resistant A. baumannii, and its combination with carbapenems may enhance in vivo efficacy.

Background: The rising incidence of fluconazole-resistant C. albicans presents a substantial challenge to global health, especially in resource-limited settings.

Aim: To delineate the proteomic and β-hydroxybutyrylome changes associated with fluconazole resistance and identify potential novel therapeutic approaches.

Methods: We performed comprehensive proteomic and β-hydroxybutyrylome analyses on fluconazole-resistant and -susceptible C. albicans strains. Lysine β-hydroxybutyrylation levels were quantified using Western blotting (WB), and the synergistic interactions between β-hydroxybutyrate (BHB) and fluconazole were evaluated through checkerboard assays.

Results: Proteomic profiling exhibited significant dysregulation of acylation-modulating enzymes, notably downregulation of histone acetyltransferase RTT109 and upregulation of deacetylase HDA1. WB confirmed pronounced suppression of β-hydroxybutyrylation in the resistant strain. Combination therapy reduced the minimum inhibitory concentration values of fluconazole and BHB by 64-fold and 4-fold, respectively, indicating a synergistic interaction. β-hydroxybutyrylome profiling identified 27 significantly upregulated sites on 27 proteins and 91 downregulated sites on 86 proteins in the resistant strain, consistent with WB data. Bioinformatic analyses implicated alterations in β-hydroxybutyrylation of metabolic pathway proteins as a key mechanism underlying the development of fluconazole resistance.

Conclusion: Fluconazole-resistant C. albicans poses a growing threat. This study links reduced β-hydroxybutyrylation to fluconazole resistance and highlights post-translational modifications as potential therapeutic targets.