Phylodemographic signatures in the emergence of community-associated MRSA

Authors: STEINIG, EIKE - UNIVERSITY OF MELBOURNE; AGLUA, IZZARD - JAMES COOK UNIVERSITY; DUCHENE, SEBASTIAN - UNIVERSITY OF MELBOURNE; MEEHAN, MICHAEL - JAMES COOK UNIVERSITY; YOANNES, MITION - PAPUA NEW GUINEA INSTITUTE OF MEDICAL RESEARCH; FIRTH, CADHLA - JAMES COOK UNIVERSITY; JAWORSKI, JAN - SIR JOSEPH NOMBRI MEMORIAL KUNDIAWA GENERAL HOSPITAL; DREKORE, JIMMY - SIMBU CHILDREN’S FOUNDATION; URAKOKO, BOHU - SIR JOSEPH NOMBRI MEMORIAL KUNDIAWA GENERAL HOSPITAL; POKA, HARRY - SIR JOSEPH NOMBRI MEMORIAL KUNDIAWA GENERAL HOSPITAL; WURR, CLIVE - GOROKA GENERAL HOSPITAL; EBOS, ERI - GOROKA GENERAL HOSPITAL; NANGEN, DAVID - GOROKA GENERAL HOSPITAL; MUELLER, ELKE - DRESDEN UNIVERSITY; MULVEY, PETER - JAMES COOK UNIVERSITY; Jackson, Charlene; BLOMFELDT, ANITA - OSLO AND AKERSHUS UNIVERSITY COLLEGE; VANGSTEIN AAMOT, HEGE - OSLO AND AKERSHUS UNIVERSITY COLLEGE; LAMAN, MOSES - PAPUA NEW GUINEA INSTITUTE OF MEDICAL RESEARCH; MANNING, LAURENS - UNIVERSITY OF WESTERN AUSTRALIA; WIRTH, THIERRY - MUSÉUM NATIONAL D’HISTOIRE NATURELLE; EARLS, MEGAN - UNIVERSITY OF DUBLIN; COLEMAN, DAVID - UNIVERSITY OF DUBLIN; GREENHILL, ANDREW - FEDERATION UNIVERSITY; FORD, REBECCA - PAPUA NEW GUINEA INSTITUTE OF MEDICAL RESEARCH; STEGGER, MARC - STATEN SERUM INSTITUTE; SYED, MUHAMMED ALI - UNIVERSITY OF HARIPUR; JAMIL, BUSHRA - BJ MICRO LAB; MONECKE, STEFAN - DRESDEN UNIVERSITY; EHRICHT, RALF - DRESDEN UNIVERSITY; SMITH, SIMON - CAIRNS AND HINTERLAND HOSPITAL AND HEALTH SERVICE; POMAT, WILLIAM - PAPUA NEW GUINEA INSTITUTE OF MEDICAL RESEARCH; HORWOOD, PAUL - JAMES COOK UNIVERSITY; TONG, STEVEN - MELBOURNE UNIVERSITY; MCBRYDE, EMMA - JAMES COOK UNIVERSITY

Submitted to: The Lancet Microbe
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/29/2022
Publication Date: 11/2/2022
Citation: Steinig, E., Aglua, I., Duchene, S., Meehan, M., Yoannes, M., Firth, C., Jaworski, J., Drekore, J., Urakoko, B., Poka, H., Wurr, C., Ebos, E., Nangen, D., Mueller, E., Mulvey, P., Jackson, C.R., Blomfeldt, A., Vangstein Aamot, H., Laman, M., Manning, L., Wirth, T., Earls, M., Coleman, D., Greenhill, A., Ford, R., Stegger, M., Syed, M., Jamil, B., Monecke, S., Ehricht, R., Smith, S., Pomat, W., Horwood, P., Tong, S., Mcbryde, E. 2022. Phylodemographic signatures in the emergence of community-associated MRSA. The Lancet Microbe. https://www.pnas.org/doi/epdf/10.1073/pnas.2204993119.
DOI: https://doi.org/10.1073/pnas.2204993119

Interpretive Summary: Staphylococcus aureus is a Gram-positive bacterium that can be commonly found on the skin or in the nasal passages of most humans and animals. It has been implicated in a number of diseases in humans ranging from minor skin infections to more serious infections such as pneumonia. Treatment of infections caused by S. aureus has been complicated by the rapid emergence of antibiotic resistance worldwide, such as community-associated methicillin-resistant S. aureus (MRSA). In this study, patterns of emergence and spread of community-associated MRSA lineages were described using sequence data from strains from the remote highlands of Papua New Guinea, northern Australia, additional strains of the Bengal Bay clone from Pakistan, and global lineage-resolved sequence data. Results from the study suggested that the emergence of community-associated MRSA and methicillin-susceptible S. aureus lineages in the late 20th century was driven by a combination of antibiotic resistant genotypes and epidemiological factors, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional human population centers. This study supports international collaborative research to monitor emergence and spread of community-associated bacterial pathogens.

Technical Abstract: Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 50 years. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast the patterns of emergence and spread of these lineages. We generated whole genome sequencing data for the Australian sequence type (ST) 93-MRSA-IV clone from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from a community cluster in Pakistan. Using lineage-resolved phylodynamic modelling, we first reconstructed the transmission dynamics of ST93. Elevated effective reproduction numbers indicating sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australia,dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Analysis of a ST772-MRSA-V cluster in Pakistan suggests that sustained transmission in the community following importation may be more common than previously thought. Applying the same phylodynamic methods to existing and lineage-resolved datasets, we identified common signatures in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia and Europe. Surges in Re were observed at the divergence of antibiotic resistant strains, coinciding with their establishment in regional population centers. Epidemic transmission was also observed amongst drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA and MSSA lineages in the late 20th century was driven by a combination of antibiotic resistant genotypes and epidemiological factors, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.