Genomic characterization of Staphylococcus aureus isolated from patients admitted to intensive care units of a tertiary care hospital: epidemiological risk of nasal carriage of virulent clone during admission

Abstract

We conducted a molecular epidemiological study of Staphylococcus aureus using whole-genome sequence data and clinical data of isolates from nasal swabs of patients admitted to the intensive care unit (ICU) of Hiroshima University hospital. The relationship between isolate genotypes and virulence factors, particularly for isolates that caused infectious diseases during ICU admission was compared with those that did not. The nasal carriage rates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) in patients admitted to the ICU were 7.0% and 20.1%, respectively. The carriage rate of community-acquired (CA)-MRSA was 2.3%, accounting for 32.8% of all MRSA isolates. Whole-genome sequencing analysis of the MRSA isolates indicated that most, including CA-MRSA and healthcare-associated (HA)-MRSA, belonged to clonal complex (CC) 8 [sequence type (ST) 8] and SCCmec type IV. Furthermore, results for three disease foci (pneumonia, skin and soft tissue infection, and deep abscess) and the assessment of virulence factor genes associated with disease conditions [bacteremia, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), and septic shock] suggested that nasal colonization of S. aureus clones could represent a risk for patients within the ICU. Particularly, MRSA/J and MSSA/J may be more likely to cause deep abscess infection; ST764 may cause ventilation-associated pneumonia, hospital-acquired pneumonia and subsequent bacteremia, and ARDS, and tst-1-positive isolates may cause DIC onset.IMPORTANCENasal colonization of MRSA in patients admitted to the intensive care unit (ICU) may predict the development of MRSA infections. However, no bacteriological data are available to perform risk assessments for Staphylococcus aureus infection onset. In this single-center 2-year genomic surveillance study, we analyzed all S. aureus isolates from nasal swabs of patients admitted to the ICU and those from the blood or lesions of in-patients who developed infectious diseases in the ICU. Furthermore, we identified the virulent clones responsible for causing infectious diseases in the ICU. Herein, we report several virulent clones present in the nares that are predictive of invasive infections. This information may facilitate the design of preemptive strategies to identify and eradicate virulent MRSA strains, reducing nosocomial infections within the ICU.

Keywords: ARGs; ICU; Staphylococcus aureus; VFGs; genomic sequence.

Fig 1

Schematic diagram of S. aureus isolation.

Fig 2

Proportion of STs of (A) MRSA and (B) MSSA isolates in each category. Arrows at both ends of the outer ring indicate CCs.

Fig 3

Proportion of SCCmec types in each category.

Fig 4

Proportion of (A) STs and (B) SCCmec types in HA-MRSA and CA-MRSA.

Fig 5

Pan-genome single nucleotide polymorphism (SNP)-based phylogenetic analysis of 583 S. aureus isolates in this study. A parsimony tree was constructed based on the pan-genome 249,203 SNP sites with branch lengths expressed in terms of changes per number of SNPs using kSNP3.021. Heatmap: column 1, presence or absence of infection; column 2, disease focus such as pneumoniae, SSTI, and deep abscess; column 3, each color represents an ST; column 4, each color represents a CC; column 5, methicillin-resistant S. aureus (MRSA; red); column 6, SCCmec types of MRSA; columns 7 and 8, the presence/absence of VFGs and ARGs, with black representing the presence of genes. MRSA/J is an MRSA clone belonging to CC8 (ST8), and SCCmec type is IVl and possesses tst-1. MSSA/J is an MSSA clone belonging to CC8 (ST8) and possesses tst-1. New York/Japan is an MRSA clone belonging to CC5 (ST5), and SCCmec type is II and possesses tst-1.

Fig 6

Characteristics of VFG or ARG patterns of representative STs of S. aureus isolates on nasal survey and infection groups. The proportion of several VFGs and ARGs of each ST is presented using heatmaps. The numbers in the heatmap columns are shown as percentages. R, MRSA; S, MSSA.

Fig 7

Characteristics of (A) ST and (B) VFG patterns of S. aureus isolates on pneumoniae, SSTI, and deep abscess. Arrows at both ends of the outer ring on (A) pie chart indicate CCs. (B) The numbers in the VFGs heatmap are shown as percentages.