Fungal pathogens pose a significant threat to global health. Aspergillus fumigatus accounts for approximately 65% of all invasive fungal infections in humans, with mortality rates from aspergillosis reaching nearly 50%. Fungal virulence in plant pathogenic fungi can be modified by mycoviruses, viruses that infect fungi. However, their impact on fungal pathogenesis in mammals has remained largely unexplored. Here, utilizing an A. fumigatus strain naturally infected with Aspergillus fumigatus polymycovirus-1M (AfuPmV-1M), we found that the mycovirus confers a significant survival advantage to the fungus under conditions of oxidative stress, heat stress, and within the murine lung. Thus, AfuPmV-1M modulates fungal fitness, resulting in increased virulence and the progression of exacerbated fungal disease. Moreover, antiviral treatment reverses the exacerbated virus-mediated virulence, representing a promising "antipathogenicity" therapy against virus-bearing pathogenic fungi. Taken together, these data suggest that mycoviruses play a significant role as "backseat drivers" in human fungal diseases, presenting critical clinical implications.

Acne vulgaris is a common neutrophil-driven inflammatory skin disorder in which Cutibacterium acnes (C. acnes) is known to play a key role. For decades, antibiotics have been widely employed to treat acne vulgaris, inevitably resulting in increased bacterial antibiotic resistance. Phage therapy is a promising strategy to combat the growing challenge of antibiotic-resistant bacteria, utilizing viruses that specifically lyse bacteria. Herein, we explore the feasibility of phage therapy against C. acnes. Eight novel phages, isolated in our laboratory, and commonly used antibiotics eradicate 100% of clinically isolated C. acnes strains. Topical phage therapy in a C. acnes-induced acne-like lesions mouse model affords significantly superior clinical and histological scores. Moreover, the decrease in inflammatory response was reflected by the reduced expression of chemokine CXCL2, neutrophil infiltration, and other inflammatory cytokines when compared with the infected-untreated group. Overall, these findings indicate the potential of phage therapy for acne vulgaris as an additional tool to conventional antibiotics.

SUMMARYAcne vulgaris is a common neutrophile-driven inflammatory skin disorder in whichCutibacterium acnes(C. acnes) bacteria play a significant role. Until now, antibiotics have been widely used to treat acne vulgaris, with the inevitable increase in bacterial antibiotic resistance. Phage therapy is a promising solution to the rising problem of antibiotic-resistant bacteria, utilizing viruses that specifically lyse bacteria.Here, we explored the feasibility of phage therapy againstC. acnes. By combining eight novel phages we had isolated, together with commonly used antibiotics, we achieved 100% eradication of clinically isolatedC. acnesstrains. Using topical phage therapy in an acne mouse model resulted in significantly superior clinical scores, as well as a reduction in neutrophil infiltration compared to the control group. These results demonstrate the potential of phage therapy in acne vulgaris treatment, especially when antibiotic-resistant strains are involved.

Abstract Acne vulgaris is a common neutrophil-driven inflammatory skin disorder in which Cutibacterium acnes (C. acnes) plays a significant role. For decades antibiotics have been widely used to treat acne vulgaris, with the inevitable increase in bacterial antibiotic resistance.Phage therapy is a promising solution to the rising problem of antibiotic-resistant bacteria, utilizing viruses that specifically lyse bacteria.Here, we explored the feasibility of phage therapy against C. acnes. Combining eight novel phages we had isolated and commonly used antibiotics, 100% of clinically isolated C. acnes strains were eradicated.Using topical phage therapy in a C. acnes-induced acne-like lesions mouse model resulted in significantly superior clinical and histological scores. Moreover, the inflammatory response decreased as reflected by reducing the chemokine CXCL2, infiltration of neutrophils, and other inflammatory cytokines, compared to the untreated group.These results demonstrate the potential of phage therapy in acne vulgaris treatment, especially when antibiotic-resistant strains are involved.

OPINION article Front. Cell. Infect. Microbiol., 13 October 2022Sec. Fungal Pathogenesis Volume 12 - 2022 | https://doi.org/10.3389/fcimb.2022.1020608

Antibiotic-resistant Cutibacterium acnes has been reported worldwide, but data from Israeli patients with acne is currently lacking. This study evaluated the antibiotic susceptibility of C. acnes, isolated from 50 Israeli patients with acne to commonly prescribed antibiotics, using the Epsilometer test (E-test). Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis, 16S rRNA sequencing and single locus sequence typing (SLST) molecular typing were used to identify and characterize C. acnes. Among 36 strains isolated, phylotype IA1 was most common. Resistance to at least one antibiotic was found in 30.6% of tested strains. Resistance rates were highest for erythromycin (25.0%), followed by doxycycline (19.4%), clindamycin (16.7%), minocycline (11.1%) and tetracycline (8.3%). Significant correlation was found between resistance to multiple antibiotics, with 5.6% of isolates resistant to all antibiotics tested. When reviewing resistances rate worldwide antibiotic resistance was found to be prevalent in Israel. Measures to limit the emergence of antibiotic-resistant strains of Cutibacterium acnes should be taken and alternative treatments should be sought.

Clinical applications of bacteriophage therapy have been recently gathering significant attention worldwide, used mostly as rescue therapy in cases of near-fatal antibiotic failure. Thus, clinically relevant in-vivo models presenting both short- and long-term implications of phage therapy given as rescue treatment for fulminant infections are of highest importance. In this study, a cocktail consisting of two lytic bacteriophages was used to evaluate the therapeutic efficacy of phage therapy as a rescue treatment for severe septic peritonitis in a mouse model. We established that a single injection of the bacteriophage cocktail was sufficient to completely reverse a 100% mortality trend caused by Vancomycin-Resistant Enterococcus faecalis, with significant improvement in both the clinical state and laboratory test results, and without harmful effects on the microbiome. The combination of bacteriophages with a suboptimal antibiotic regimen imparts an additional beneficial effect on the treatment success.

Aim. The detection of the ability of S. aureus strains isolated from human upper airways to β-lactamase production and determination of the effect of p-dimethylaminobenzaldehyde isonicotinoylhydrazone and Sn(IV) complex with 2-hydroxyinaphtaldehyde isonicotinoylhydrazone on the sensitivity of lactamase-producing strains to penicillin. Methods. We have used the microbiological methods: disc-diffusion, double-disc and serial dilution methods and statistical data analysis. Results. 33 S. aureus strains with the highest resistance to penicillins and III-IV generation cephalosporins have been isolated from the upper airways of healthy people. The ability to synthesize β-lactamases has been detected in 5 strains. It has been shown 32-fold decrease of MIC of penicillin for S. aureus 17 in the presence of studied hydrazone and Sn (IV) complex. Conclusions. Studied hydrazone and Sn (IV) complex have the potential ability to overwhelm the resistance of Gram-positive bacteria to β-lactam antibiotics.