Alison Coady

We conducted a literature review to evaluate global antifungal susceptibility patterns in Candida auris, an emerging multidrug-resistant fungal pathogen of growing clinical concern. A comprehensive search of the literature identified 29 studies reporting min-imum inhibitory concentrations (MICs) and resistance rates across major antifungal classes. Across studies, C. auris demonstrated consistently high resistance to fluconazole, with variable resistance observed among other azoles, amphotericin B, and echi-nocandins, alongside evidence of emerging multidrug resistance. These findings reflect significant geographic variability and highlight ongoing challenges in treatment selec-tion due to inconsistent susceptibility profiles and limited standardized breakpoints. Emerging antifungal agents, including ibrexafungerp and manogepix, demonstrate promising activity and may help address current therapeutic gaps. Overall, the global rise in antifungal resistance among C. auris isolates underscores the narrowing range of effective therapeutic options and reinforces the need for continued surveillance, improved susceptibility testing standardization, and development of novel antifungal agents.

Urinary tract infections (UTIs) are common in children and are predominantly caused by uropathogenic Escherichia coli (UPEC). An increasing proportion of these strains produce extended-spectrum β-lactamases (ESBLs), which render β-lactam antibiotics ineffective. Interestingly, some patients with ESBL-producing UTIs improve clinically following treatment with antibiotics like cephalexin, despite demonstrated in vitro resistance. Working alongside and at times synergistically with antibiotics, host immune factors, such as the antimicrobial peptide cathelicidin (LL-37), contribute to bacterial clearance through direct killing and inhibition of biofilm formation. In this review, we summarize the current understanding of pediatric ESBL-producing UPEC infections and present selected in vitro and in vivo experimental data evaluating the combined effects of LL-37 and cephalexin on clinical isolates. Although no synergy was observed, ESBL-producing isolates demonstrated reduced bacterial burden in vivo compared to a non-ESBL UPEC strain. These findings suggest that host immune factors and environmental conditions may influence the fitness and virulence of drug-resistant UTI pathogens, warranting further investigation.

Manganese plays a central role in cellular detoxification of reactive oxygen species (ROS). Therefore, manganese acquisition is considered to be important for bacterial pathogenesis by counteracting the oxidative burst of phagocytic cells during host infection. However, detailed analysis of the interplay between bacterial manganese acquisition and phagocytic cells and its impact on bacterial pathogenesis has remained elusive for Staphylococcus aureus, a major human pathogen. Here, we show that a mntC mutant, which lacks the functional manganese transporter MntABC, was more sensitive to killing by human neutrophils but not murine macrophages, unless the mntC mutant was pre-exposed to oxidative stress. Notably, the mntC mutant formed strikingly small colonies when recovered from both type of phagocytic cells. We show that this phenotype is a direct consequence of the inability of the mntC mutant to reinitiate growth after exposure to phagocytic oxidative burst. Transcript and quantitative proteomics analyses revealed that the manganese-dependent ribonucleotide reductase complex NrdEF, which is essential for DNA synthesis and repair, was highly induced in the mntC mutant under oxidative stress conditions including after phagocytosis. Since NrdEF proteins are essential for S. aureus viability we hypothesize that cells lacking MntABC might attempt to compensate for the impaired function of NrdEF by increasing their expression. Our data suggest that besides ROS detoxification, functional manganese acquisition is likely crucial for S. aureus pathogenesis by repairing oxidative damages, thereby ensuring efficient bacterial growth after phagocytic oxidative burst, which is an attribute critical for disseminating and establishing infection in the host.