Search Results (53)

Background: An imbalance in the vaginal microbiota, often characterized by reduced lactobacilli, paves the way forth for opportunistic bacteria from the gastrointestinal tract. The presence of aerobic bacteria in the genital tract during pregnancy can have negative outcomes on the pregnancy. Peripartum infections, when not adequately managed, can significantly impact maternal and neonatal health. Antimicrobial resistance poses an escalating global health threat, with newborns particularly vulnerable. Methods: This study constitutes a retrospective observational analysis, encompassing all microbial strains isolated from pregnant women admitted to the “Pius Brînzeu” Clinical County Emergency Hospital in Timișoara, Romania for various infectious diseases over one year. We analyzed 274 samples from 246 pregnant women, of which 242 were cervical samples, 23 urine cultures, 3 wound secretions, 3 amniotic fluids, 1 peritoneal cavity fluid, 1 sputum, and 1 hemoculture. Results: In cervical samples, Group B Streptococcus (GBS) was the most prevalent, representing 42.46% of the isolates. E. coli was the second most frequent at 30.16%, followed by K. pneumoniae at 11.9%, S. aureus at 8.73%, C. albicans at 2.78%, and other species at 3.97%. A total of 9.63% of cervical GBS isolates exhibited resistance to penicillin, while 23.36% were identified as multi-drug resistant (MDR). Methicillin-resistant S. aureus (MRSA) and MDR S. aureus strains were identified in 50% and 54.54% of the S. aureus-positive cervical samples, respectively. Conclusions: Recognizing the implications of maternal infection or colonization, especially with antimicrobial resistance bacteria, aids in assessing risks during pregnancy. Full article

Background/Objectives: Although a “forgotten” disease in developed countries, typhoid fever remains a significant global health problem, especially in regions with inadequate sanitation and overcrowding. Despite medical advances, this systemic bacterial infection, caused by Salmonella Typhi, continues to affect millions worldwide. Accurate diagnosis and timely treatment are crucial to prevent severe complications and mortality. Even though antibiotic therapy is effective, the emergence of drug-resistant strains is a growing challenge. Methods: We present a series of cases encountered in a tertiary infectious disease hospital in Romania over 15 years. Results: The hospitalised patients were mainly from Sub-Saharan Africa and the Indian subcontinent; the median time between the onset of the first symptoms and hospital admission was 15 days. The symptoms encountered along with fever were headache, chills, cough, diarrhoea and tachycardia, an unusual feature in the clinical picture of this disease. Aneosinophilia (the absence of peripheral eosinophilic granulocytes) was the most frequently encountered laboratory finding, followed by increased serum transaminases and inflammatory syndrome. Conclusions: S. Typhi was generally identified from blood culture, demonstrating, except in one case, resistance to ciprofloxacin and, in several cases, multi-drug resistance (MDR). In this series of cases, all strains were sensitive to ceftriaxone. Full article

Tuberculosis (TB) remains one of the most challenging infectious diseases, with Mycobacterium tuberculosis (Mtb) employing sophisticated mechanisms to evade host immunity and establish persistent infections. This review explores recent advances in understanding Mtb’s immune evasion strategies; granuloma dynamics; and emerging immunotherapeutic approaches. Key findings highlight the manipulation of host autophagy; metabolic reprogramming; and cytokine pathways by Mtb to sustain its survival within host cells. Insights into granuloma formation reveal the critical role of bacterial lipids; immune modulation; and hypoxia-driven dormancy in maintaining chronic infection. Innovative therapeutic strategies, including host-directed therapies; epigenetic interventions; and immunomodulators, hold promise for improving TB management and combating drug-resistant strains. Despite these advancements, significant challenges remain, including the development of effective vaccines; addressing latent TB; and ensuring equitable access to novel treatments. The integration of advanced technologies such as artificial intelligence and multi-omics approaches, alongside global collaboration, is essential to overcome these hurdles. This review underscores the importance of a multidisciplinary approach to tackling TB, with the ultimate goal of eradicating this global health threat. Full article

Background/Objectives: Infectious diseases caused by Staphylococcus aureus (S. aureus) have become alarming health issues worldwide due to the ever-increasing emergence of multidrug resistance. In silico approaches can accelerate the identification and/or design of versatile antibacterial chemicals with the ability to target multiple S. aureus strains with varying degrees of drug resistance. Here, we develop a perturbation theory machine learning model based on a multilayer perceptron neural network (PTML-MLP) for the prediction and design of versatile virtual inhibitors against S. aureus strains. Methods: To develop the PTML-MLP model, chemical and biological data associated with antibacterial activity against S. aureus strains were retrieved from the ChEMBL database. We applied the Box–Jenkins approach to convert the topological indices into multi-label graph-theoretical indices; the latter were used as inputs for the creation of the PTML-MLP model. Results: The PTML-MLP model exhibited accuracy higher than 80% in both training and test sets. The physicochemical and structural interpretation of the PTML-MLP model was performed through the fragment-based topological design (FBTD) approach. Such interpretations permitted the analysis of different molecular fragments with favorable contributions to the multi-strain antibacterial activity and the design of four new drug-like molecules using different fragments as building blocks. The designed molecules were predicted/confirmed by our PTML model as multi-strain inhibitors of diverse S. aureus strains, thus representing promising chemotypes to be considered for future synthesis and biological testing of versatile anti-S. aureus agents. Conclusions: This work envisages promising applications of PTML modeling for early antibacterial drug discovery and related antimicrobial research areas. Full article

With the goal of fast and accurate diagnosis of infectious diseases, this study presents a novel electrochemical biosensor that employs a refined aptamer (C9t) for the detection of spike (S) protein SARS-CoV-2 variants in a flexible multielectrode aptasensor array with PoC capabilities. Two aptamer modifications were employed: removing the primer binding sites and including two dithiol phosphoramidite anchor molecules. Thus, reducing fabrication time from 24 to 3 h and increasing the stability and sparseness for multi-thiol aptasensors compared to a standard aptasensor using single thiols, without a reduction in aptamer density. The biosensor fabrication, optimization, and detection were verified in detail by electrochemistry, QCM-D, SPR, and XPS. The analyte–receptor binding was further confirmed spectroscopically at the level of individual molecules by AFM-IR. The aptasensor possesses a low limit of detection (8.0 fg/mL), the highest sensitivity reported for S protein (209.5 signal per concentration decade), and a wide dynamic detection range (8.0 fg/mL–38 ng/mL) in nasopharyngeal samples, covering the clinically relevant range. Furthermore, the C9t aptasensor showed high selectivity for SARS-CoV-2 S proteins over biomarkers for MERS-CoV, RSV, and Influenza. Even more, it showed a three times higher sensitivity for the Omicron in comparison to the Wuhan strain (wild type), alpha, and beta variants of the SARS-CoV-2 virus. Those results demonstrate the creation of an affordable and variant-selective refined C9t aptasensor that outperformed current rapid diagnosis tests. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a critical global health threat, leading to increased morbidity, mortality, and healthcare costs. This study aimed to identify the most common bacterial pathogens and their resistance profiles from 2179 positive clinical cultures from inpatients at “Victor Babes” Hospital of Infectious Disease and Pneumoftiziology Timisoara in 2023. Methods: Samples were collected from sputum, bronchial aspiration, hemoculture, urine, wound secretions, catheter samples, and other clinical specimens. Results: Key pathogens identified included Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii, with notable resistance patterns, observed K. pneumoniae exhibited high resistance rates, notably 41.41% in Quarter 1, while E. coli showed 35.93% resistance in the same period. S. aureus, particularly MRSA, remained a persistent challenge, with 169 cases recorded over the year. A. baumannii and P. aeruginosa displayed alarming levels of multi-drug resistance, especially in Quarter 3 (88.24% and 22.02%, respectively). Although there was a general decline in resistance rates by Quarter 4, critical pathogens such as S. aureus and K. pneumoniae continued to exhibit significant resistance (81.25% and 21.74%, respectively). Conclusions: The study’s findings align with the broader antimicrobial resistance trends observed in Romania, where high resistance rates in K. pneumoniae, E. coli, S. aureus (MRSA), Acinetobacter, and Pseudomonas species have been widely reported, reflecting the country’s ongoing struggle with multi-drug-resistant infections. Despite some reductions in resistance rates across quarters, the persistent presence of these resistant strains underscores the critical need for strengthened antimicrobial stewardship, infection control measures, and continuous surveillance to combat the growing threat of AMR in Romania and similar healthcare settings. Full article

Background/Objectives. The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen, causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit the growth or impair the survival of bacterial pathogens. Given their large structural and chemical diversity, as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against Gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin-resistant S. aureus (MRSA) and the multi-drug-resistant community-acquired strain USA300LAC. Methods. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Results/Conclusions. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 μg/mL), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane-associated mechanism of action. Full article

The emergence and spread of drug-resistant pathogens, resulting in antimicrobial resistance, continue to compromise our capability to handle commonly occurring infectious diseases. The rapid global spread of multi-drug-resistant pathogens, particularly systemic fungal infections, presents a significant concern, as existing antimicrobial drugs are becoming ineffective against them. In recent decades, there has been a notable increase in systemic fungal infections, primarily caused by Candida species, which are progressively developing resistance to azoles. Moreover, Candida species biofilms are among the most common in clinical settings. In particular, they adhere to biomedical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. In recent years, many research programs have concentrated on the development of novel compounds with possible antimicrobial effects to address this issue, and new sources, such as plant-derived antimicrobial compounds, have been thoroughly investigated. Essential oils (EOs), among their numerous pharmacological properties, exhibit antifungal, antibacterial, and antiviral activities and have been examined at a global scale as the possible origin of novel antimicrobial compounds. A recent work carried out by our research group concerned the synergistic antibacterial activities of commercially available and chemically characterized Cinnamomum verum L. essential oil (C. verum EO) in association with sertraline, a selective serotonin reuptake inhibitor whose repositioning as a non-antibiotic drug has been explored over the years with encouraging results. The aim of this work was to explore the synergistic effects of C. verum EO with sertraline on both planktonic and sessile Candida species cells. Susceptibility testing and testing of the synergism of sertraline and C. verum EO against planktonic and sessile cells were performed using a broth microdilution assay and checkerboard methods. A synergistic effect was evident in both the planktonic cells and mature biofilms, with significant reductions in fungal viability. Indeed, the fractional inhibitory concentration index (FICI) was lower than 0.5 for all the associations, thus indicating significant synergism of the associations with the Candida strains examined. Moreover, the concentrations of sertraline able to inhibit Candida spp. strain growth and biofilm formation significantly decreased when it was used in combination with C. verum EO for all the strains considered, with a reduction percentage in the amount of each associated component ranging from 87.5% to 97%. Full article

Background and Aims: Several studies reported the effect of COVID-19 on inducing gut dysbiosis, which is also correlated with disease severity. This study aims to investigate the effect of a nutraceutical formula on the shift of microbiota profiles and, secondly, on the clinical–pathological parameters of acute and post-acute COVID-19 patients. Methods: In this randomised, double-blind, placebo-controlled trial conducted at National Institute for Infectious diseases (INMI) Lazzaro Spallanzani (Italy), 52 patients were randomly assigned (1:1) to receive a multistrain synbiotic formula (Kebirah^®) or placebo orally for 35 days at COVID-19 diagnosis. Health professionals, investigators, and patients were masked to group assignments. The V3–V4 hypervariable region of 16S rRNA gene sequencing was employed to study the gut microbiota composition in the two groups. Results: Supplementation with Kebirah^® prevented the decrease in the Shannon diversity index of gut microbiota, which was instead observed in patients receiving the placebo. In addition, decreases in lymphocyte count and haemoglobin levels were observed only in the placebo group and not in the treated group, which was also characterised by an amelioration of the gut microbial profile, with an enrichment in beneficial bacteria and a preservation of species diversity. Conclusions: Our data suggest that modulating the gut microbiota in acute disease through administration of a specific symbiotic formula could be a useful strategy in the frame of SARS-CoV-2 infections. Full article

Wildlife may represent an important source of infectious diseases for humans and other wild and domestic animals. Wild ruminants can harbour and transmit Shiga toxin-producing Escherichia coli (STEC) to humans, and some strains even carry important antimicrobial resistance. In this study, 289 livers of wild roe deer, fallow deer, red deer and chamois collected in Liguria, north-west Italy, from 2019 to 2023 were analysed. Overall, 44 STEC strains were isolated from 28 samples. The characterisation of serogroups showed the presence of O104, O113, O145 and O146 serogroups, although for 28 colonies, the serogroup could not be determined. The most prevalent Shiga toxin gene in isolated strains was Stx2, and more specifically the subtype Stx2b. The other retrieved subtypes were Stx1a, Stx1c, Stx1d and Stx2g. The isolated strains generally proved to be susceptible to the tested antimicrobials. However, multi-drug resistances against highly critical antimicrobials were found in one strain isolated from a roe deer. This study highlights the importance of wildlife monitoring in the context of a “One Health” approach. Full article

Streptococcus gordonii is a gram-positive, mutualistic bacterium found in the human body. It is found in the oral cavity, upper respiratory tract, and intestines, and presents a serious clinical problem because it can lead to opportunistic infections in individuals with weakened immune systems. Streptococci are the most prevalent inhabitants of oral microbial communities, and are typical oral commensals found in the human oral cavity. These streptococci, along with many other oral microbes, produce multispecies biofilms that can attach to salivary pellicle components and other oral bacteria via adhesin proteins expressed on the cell surface. Antibiotics are effective against this bacterium, but resistance against antibodies is increasing. Therefore, a more effective treatment is needed. Vaccines offer a promising method for preventing this issue. This study generated a multi-epitope vaccine against Streptococcus gordonii by targeting the completely sequenced proteomes of five strains. The vaccine targets are identified using a pangenome and subtractive proteomic approach. In the present study, 13 complete strains out of 91 strains of S. gordonii are selected. The pangenomics results revealed that out of 2835 pan genes, 1225 are core genes. Out of these 1225 core genes, 643 identified as non-homologous proteins by subtractive proteomics. A total of 20 essential proteins are predicted from non-homologous proteins. Among these 20 essential proteins, only five are identified as surface proteins. The vaccine construct is designed based on selected B- and T-cell epitopes of the antigenic proteins with the help of linkers and adjuvants. The designed vaccine is docked against TLR2. The expression of the protein is determined using in silico gene cloning. Findings concluded that Vaccine I with adjuvant shows higher interactions with TLR2, suggesting that the vaccine has the ability to induce a humoral and cell-mediated response to treat and prevent infection; this makes it promising as a vaccine against infectious diseases caused by S. gordonii. Furthermore, validation of the vaccine construct is required by in vitro and in vivo trials to check its actual potency and safety for use to prevent infectious diseases caused by S. gordonii. Full article

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing. Full article

Pseudorabies is an acute and febrile infectious disease caused by pseudorabies virus (PRV), a member of the family Herpesviridae. Currently, PRV is predominantly endemoepidemic and has caused significant economic losses among domestic pigs. Other animals have been proven to be susceptible to PRV, with a mortality rate of 100%. In addition, 30 human cases of PRV infection have been reported in China since 2017, and all patients have shown severe neurological symptoms and eventually died or developed various neurological sequelae. In these cases, broad-spectrum anti-herpesvirus drugs and integrated treatments were mostly applied. However, the inhibitory effect of the commonly used anti-herpesvirus drugs (e.g., acyclovir, etc.) against PRV were evaluated and found to be limited in this study. It is therefore urgent and important to develop drugs that are clinically effective against PRV infection. Here, we constructed a high-throughput method for screening antiviral drugs based on fluorescence-tagged PRV strains and multi-modal microplate readers that detect fluorescence intensity to account for virus proliferation. A total of 2104 small molecule drugs approved by the U.S. Food and Drug Administration (FDA) were studied and validated by applying this screening model, and 104 drugs providing more than 75% inhibition of fluorescence intensity were selected. Furthermore, 10 drugs that could significantly inhibit PRV proliferation in vitro were strictly identified based on their cytopathic effects, virus titer, and viral gene expression, etc. Based on the determined 50% cytotoxic concentration (CC₅₀) and 50% inhibitory concentration (IC₅₀), the selectivity index (SI) was calculated to be 26.3–3937.2 for these 10 drugs, indicating excellent drugability. The antiviral effects of the 10 drugs were then assessed in a mouse model. It was found that 10 mg/kg brincidofovir administered continuously for 5 days provided 100% protection in mice challenged with lethal doses of the human-origin PRV strain hSD-1/2019. Brincidofovir significantly attenuated symptoms and pathological changes in infected mice. Additionally, time-of-addition experiments confirmed that brincidofovir inhibited the proliferation of PRV mainly by interfering with the viral replication stage. Therefore, this study confirms that brincidofovir can significantly inhibit PRV both in vitro and in vivo and is expected to be an effective drug candidate for the clinical treatment of PRV infections. Full article

Global health faces a significant issue with the rise of infectious diseases caused by bacteria, fungi, viruses, and parasites. The increasing number of multi-drug resistant microbial pathogens severely threatens public health worldwide. Antibiotic-resistant pathogenic bacteria, in particular, present a significant challenge. Therefore, there is an urgent need to identify new potential antimicrobial targets and discover new chemical entities that can potentially reverse bacterial resistance. The main goal of this research work was to create and develop a library of 3,6-disubstituted xanthones based on twin drugs and molecular extension approaches to inhibit the activity of efflux pumps. The process involved synthesizing 3,6-diaminoxanthones through the reaction of 9-oxo-9H-xanthene-3,6-diyl bis(trifluoromethanesulfonate) with various primary and secondary amines. The resulting 3,6-disubstituted xanthone derivatives were then tested for their in vitro antimicrobial properties against a range of pathogenic strains and their efficacy in inhibiting the activity of efflux pumps, biofilm formation, and quorum-sensing. Several compounds have exhibited effective antibacterial properties against the Gram-positive bacterial species tested. Xanthone 16, in particular, has demonstrated exceptional efficacy with a remarkable MIC of 11 µM (4 µg/mL) against reference strains Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212, and 25 µM (9 µg/mL) against methicillin-resistant S. aureus 272123. Furthermore, some derivatives have shown potential as antibiofilm agents in a crystal violet assay. The ethidium bromide accumulation assay pinpointed certain compounds inhibiting bacterial efflux pumps. The cytotoxic effect of the most promising compounds was examined in mouse fibroblast cell line NIH/3T3, and two monoamine substituted xanthone derivatives with a hydroxyl substituent did not exhibit any cytotoxicity. Overall, the nature of the substituent was critical in determining the antimicrobial spectra of aminated xanthones. Full article

Background: The increase of multi-resistant bacteria, especially Staphylococcus spp. and Enterobacteriaceae, constitutes a challenge in veterinary medicine. The rapid growth of resistance is outpacing antibiotic discovery. Innovative strategies are needed, including the use of natural products like Allium species (Allium sativum L. and Allium cepa L.), which have been used empirically for centuries to treat infectious diseases in humans and farm and aquaculture animals due to their antibacterial properties. Methods: This study aimed to evaluate the in vitro activity of two Allium-derived compounds, propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO), against multi-resistant Staphylococcus spp. (n = 30) and Enterobacteriaceae (n = 26) isolated from dogs referred to a veterinary teaching hospital in Madrid. Results and Discussion: The results indicated the in vitro efficacy of PTSO/PTS against the tested bacterial strains, and 56.7% of Staphylococcus pseudintermedius and 53.8% of Enterobacteriaceae showed sensitivity to PTS and PTSO compared with classic antibiotics. In addition, 50% of S. pseudintermedius strains resistant to erythromycin, ibofloxacin, difloxacin and orbifloxacin and 50% of Enterobacteriaceae strains resistant to tetracycline and doxycycline were sensitive to PTS and PTSO. Although studies are needed to verify their efficacy in vivo, the combined use of PTS and PTSO exhibits promise in enhancing bacterial sensitivity against S. pseudintermedius and Enterobacteriaceae infections, providing a first insight into the potential of both compounds in veterinary practice. Full article