High Incidence of Metastatic Infections in Panton-Valentine Leucocidin-Negative, Community-Acquired Methicillin-Resistant Staphylococcus aureus Bacteremia: An 11-Year Retrospective Study in Japan.

Panton-Valentine leucocidin (PVL)-negative community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was originally disseminated in Japan and has since replaced healthcare-associated MRSA (HA-MRSA). However, the clinical characteristics of CA-MRSA bacteremia (CA-MRSAB) compared with those of HA-MRSA bacteremia (HA-MRSAB) are unknown. We aim to clarify differences and investigate associations between the clinical manifestations and virulence genes associated with plasma-biofilm formation in PVL-negative CA-MRSA. From 2011 to 2021, when CA-MRSA dramatically replaced HA-MRSA, 79 MRSA strains were collected from blood cultures and analyzed via SCCmec typing and targeted virulence gene (lukSF-PV, cna, and fnbB) detection. The incidence of metastatic infection was significantly higher in CA-MRSAB than in HA-MRSAB. PVL genes were all negative, although cna and fnbB were positive in 55.6% (20/36) and 50% (18/36) of CA-MRSA strains and 3.7% (1/27) and 7.4% (2/27) of HA-MRSA strains, respectively. cna and fnbB carriage were not associated with the development of metastatic infections in MRSAB; however, the bacteremia duration was significantly longer in CA-MRSAB harboring cna. CA-MRSAB may be more likely to cause metastatic infections than HA-MRSAB. Since CA-MRSA is dominant in Japan, suspected metastatic infection foci should be identified by computed tomography, magnetic resonance imaging, and echocardiography when treating MRSAB.

A novel hamster model of SARS-CoV-2 respiratory infection using a pseudotyped virus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a biosafety level (BSL)-3 pathogen; therefore, its research environment is limited. Pseudotyped viruses that mimic the infection of SARS-CoV-2 have been widely used for in vitro evaluation because they are available in BSL-2 containment laboratories. However, in vivo application is inadequate. Therefore, animal models instigated with animal BSL-2 will provide opportunities for in vivo evaluation. Hamsters (6-10-week-old males) were intratracheally inoculated with luciferase-expressing vesicular stomatitis virus (VSV)-based SARS-CoV-2 pseudotyped virus. The lungs were harvested 24-72 h after inoculation and luminescence was measured using an in vivo imaging system. Lung luminescence after inoculation with the SARS-CoV-2 pseudotyped virus increased in a dose-dependent manner and peaked at 48 h. The VSV-G (envelope G) pseudotyped virus also induced luminescence; however, a 100-fold concentration was required to reach a level similar to that of the SARS-CoV-2 pseudotyped virus. The SARS-CoV-2 pseudotyped virus is applicable to SARS-CoV-2 respiratory infections in a hamster model. Because of the single-round infectious virus, the model can be used to study the steps from viral binding to entry, which will be useful for future research on SARS-CoV-2 entry without using live SARS-CoV-2 or transgenic animals.

Novel super-neutralizing antibody UT28K is capable of protecting against infection from a wide variety of SARS-CoV-2 variants.

Many potent neutralizing SARS-CoV-2 antibodies have been developed and used for therapies. However, the effectiveness of many antibodies has been reduced against recently emerging SARS-CoV-2 variants, especially the Omicron variant. We identified a highly potent SARS-CoV-2 neutralizing antibody, UT28K, in COVID-19 convalescent individuals who recovered from a severe condition. UT28K showed efficacy in neutralizing SARS-CoV-2 in an in vitro assay and in vivo prophylactic treatment, and the reactivity to the Omicron strain was reduced. The structural analyses revealed that antibody UT28K Fab and SARS-CoV-2 RBD protein interactions were mainly chain-dominated antigen-antibody interactions. In addition, a mutation analysis suggested that the emergence of a UT28K neutralization-resistant SARS-CoV-2 variant was unlikely, as this variant would likely lose its competitive advantage over circulating SARS-CoV-2. Our data suggest that UT28K offers potent protection against SARS-CoV-2, including newly emerging variants.