ABSTRACT
Cutaneous Leishmaniasis (CL) is a neglected tropical disease, classified by the World Health Organization (WHO) as one of the most unrestrained diseases. The Syrian war and the significant displacement of refugees aggravated the spread of this ailment into several neighboring countries in the Eastern Mediterranean Region (EMR). In Syria, Leishmania tropica is identified as one of the most aggressive and endemic identified species, causing localized or generalized lesions, often chronic or relapsing. Pentavalent antimonial drugs are currently used as first line treatment against CL. Nonetheless, these drugs exhibit several limitations, including the repetitive painful injections, high cost, poor availability, and mainly systemic toxicity. Besides, the emergence of acquired parasitic resistance hinders their potency, stressing the need for new therapies to combat CL. Natural products (NPs) epitomize a valuable source in drug discovery. NPs are secondary metabolites (SMs) produced by plants, sponges, or a wide variety of organisms, including environmental microorganisms. The EMR is characterized by its immense biodiversity, yet it remains a relatively untapped area in drug discovery. NPs of the region were explored over the last 2 decades, but their discoveries lack biogeographical diversity and are limited to the Red Sea. Here, we isolated previously uncultured environmental soil-dwelling Streptomyces sp. HAS1, from Hasbaya region in southeast Lebanon. When fermented in one of our production media named INA, HAS1 produced a crude extract with significant potency against a clinical Leishmania tropica isolate. Using bio-guided fractionation, the bioactive compound was purified and the structure was elucidated by NMR and LC-HRMS. Our findings establish NPs as strong candidates for treating Leishmania tropica and further dwells on the importance of these natural sources to combat microbial infections.
ABSTRACT
Previous studies have suggested a link between urinary tract infections (UTIs) and cognitive impairment. One possible contributing factor for UTI-induced cognitive changes that has not yet been investigated is a potential alteration in hippocampal neurogenesis. In this study, we aim to investigate the effect of UTI on brain plasticity by specifically examining alterations in neurogenesis. Adult male Sprague Dawley rats received an intra-urethral injection of an Escherichia coli (E. coli) clinical isolate (108 CFU/mL). We found that rats with a UTI (CFU/mL ≥ 105) had reduced proliferation of neural stem cells (NSCs) at an early time point post infection (day 4) and neurogenesis at a later time point (day 34). This was associated with the decreased expression in mRNA of BDNF, NGF, and FGF2, and elevated expression of IL-1ß in the hippocampus at 6 h post infection, but with no changes in optical intensity of the microglia and astrocytes. In addition, infected rats spent less time exploring a novel arm in the Y-maze test. Treatment with an anti-inflammatory drug did not revert the effect on NSCs, while treatment with antibiotics further decreased the basal level of their proliferation. This study presents novel findings on the impact of urinary tract infections on hippocampal neurogenesis that could be correlated with cognitive impairment.
ABSTRACT
INTRODUCTION: Infections caused by extensively-drug resistant (XDR) and pan-drug resistant (PDR) Klebsiella pneumoniae represent an emerging threat due to the high associated mortality. This study aimed to characterize two carbapenem resistant K. pneumoniae strains from the same patient, the first being PDR (referred to as IMP 1078b) and the second being XDR (referred to IMP 1078s) isolated from the same patient. METHODOLOGY: Antimicrobial susceptibility testing was done for the 2 K. pneumoniae isolates, followed by carbapenem/ß-lactamase inhibitor combination assay, and fitness cost against cefepime and meropenem. Then, whole-genome sequence analysis was performed to decipher the molecular mechanisms behind the high level of resistance recorded in both isolates. Finally, qRT-PCR was done for ß-lactam resistant genes. RESULTS: This is the first report about a K. pneumoniae isolate harboring 47 antimicrobial resistance genes and having type IV pilli (Yersinia) and the fimbrial adherence determinant Stb (Salmonella) as virulence factors. Further analysis on both isolates are discussed within the article. CONCLUSION: The co-existence of a high number of antimicrobial resistant (AMR) genes and virulence factor genes may lead to a life threatening invasive and untreatable infection.
