Methicillin-Resistant Staphylococcus aureus from Peninsular Malaysian Animal Handlers: Molecular Profile, Antimicrobial Resistance, Immune Evasion Cluster and Genotypic Categorization

Staphylococcus aureus (S. aureus) infections, particularly methicillin-resistant Staphylococcus aureus (MRSA) in humans and animals, have become a significant concern globally. The present study aimed to determine the prevalence and antibiogram of S. aureus isolated from animal handlers in Peninsular Malaysia. Furthermore, the genotypic characteristics of S. aureus isolates were also investigated. Nasal and oral swab samples were collected from 423 animal handlers in Peninsular Malaysia. The antibiogram profiles of S. aureus against 18 antibiotics were established using a Kirby–Bauer test. The genotypic profile of S. aureus, including the presence of antimicrobial resistance (AMR), virulence genes and spa genotypes, was investigated using molecular techniques. The overall carriage rate of S. aureus, MRSA and MDRSA was 30.5%, 1.2% and 19.4%, respectively. S. aureus was highly resistant against penicillin (72.3%) and amoxicillin (52.3%). Meanwhile, gentamicin and linezolid were fully effective against all the isolated S. aureus from animal handlers. It was observed that animal handlers with close exposure to poultry were more likely to carry S. aureus that is resistant to tetracycline and erythromycin. S. aureus isolates harboured tetracycline resistance (tetK, tetL and tetM), erythromycin resistance (ermA, ermB, ermC and msrA) and immune evasion cluster (IEC) genes (scn, chp, sak, sea and sep). Seventeen different spa types were detected among the 30 isolates of MDRSA, with t189 (16.7%) and t4171 (16.7%) being the predominant spa type, suggesting wide genetic diversity of the MDRSA isolates. The present study demonstrated the prevalence of S. aureus strains, including MRSA and MDRSA with various antimicrobial resistance and genetic profiles from animal handlers in Peninsular Malaysia.

SARS-CoV-2 Omicron Outbreak in a Dormitory in Saint-Petersburg, Russia

The B.1.1.529 Omicron variant of SARS-CoV-2 is rapidly spreading, displacing the globally prevalent Delta variant. Before December 16, 2021, community transmission had already been observed in tens of countries globally. However, in Russia, all reported cases had been sporadic and associated with travel. Here, we report an Omicron outbreak at a students’ dormitory in Saint Petersburg, Russia. Out of the 462 sampled residents of the dormitory, 206 (44.6%) tested PCR positive, and 159 (77.1%) of these infections carried the S:ins214EPE insertion, indicating that they were of the Omicron strain. 104 (65%) of Omicron-positive patients have been vaccinated and/or reported previous covid-19. Whole genome sequencing confirmed that the outbreak is caused by the Omicron variant. Phylogenetic analysis showed that the outbreak has a single origin, and belongs to the S:346K sublineage of Omicron which may be characterized by an increased rate of spread, compared to other Omicron sublineages. The rapid spread of Omicron in a population with preexisting immunity to previous variants underlines its propensity for immune evasion.

Host-Adapted Gene Families Involved in Murine Cytomegalovirus Immune Evasion

Cytomegaloviruses (CMVs) are host species-specific and have adapted to their respective mammalian hosts during co-evolution. Host-adaptation is reflected by “private genes” that have specialized in mediating virus-host interplay and have no sequence homologs in other CMV species, although biological convergence has led to analogous protein functions. They are mostly organized in gene families evolved by gene duplications and subsequent mutations. The host immune response to infection, both the innate and the adaptive immune response, is a driver of viral evolution, resulting in the acquisition of viral immune evasion proteins encoded by private gene families. As the analysis of the medically relevant human cytomegalovirus by clinical investigation in the infected human host cannot make use of designed virus and host mutagenesis, the mouse model based on murine cytomegalovirus (mCMV) has become a versatile animal model to study basic principles of in vivo virus-host interplay. Focusing on the immune evasion of the adaptive immune response by CD8+ T cells, we review here what is known about proteins of two private gene families of mCMV, the m02 and the m145 families, specifically the role of m04, m06, and m152 in viral antigen presentation during acute and latent infection.

Molecular basis of SARS-CoV-2 Omicron variant receptor engagement and antibody evasion and neutralization

The SARS-CoV-2 Omicron variant exhibits striking immune evasion and is spreading globally at an unprecedented speed. Understanding the underlying structural basis of the high transmissibility and greatly enhanced immune evasion of Omicron is of high importance. Here through cryo-EM analysis, we present both the closed and open states of the Omicron spike, which appear more compact than the counterparts of the G614 strain, potentially related to the Omicron substitution induced enhanced protomer-protomer and S1-S2 interactions. The closed state showing dominant population may indicate a conformational masking mechanism of immune evasion for Omicron spike. Moreover, we capture two states for the Omicron S/ACE2 complex with S binding one or two ACE2s, revealing that the substitutions on the Omicron RBM result in new salt bridges/H-bonds and more favorable electrostatic surface properties, together strengthened interaction with ACE2, in line with the higher ACE2 affinity of the Omicron relative to the G614 strain. Furthermore, we determine cryo-EM structures of the Omicron S/S3H3 Fab, an antibody able to cross-neutralize major variants of concern including Omicron, elucidating the structural basis for S3H3-mediated broad-spectrum neutralization. Our findings shed new lights on the high transmissibility and immune evasion of the Omicron variant and may also inform design of broadly effective vaccines against emerging variants.