Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter

Staphylococcus aureus is a major contributor of nosocomial infections of humans in the world. This study elucidates the genomic sequences of an MRSA (MRSA PR01) isolate from a patient with septicaemia in Kuala Lumpur, a clinical methicillinsusceptible S. aureus (MSSA) isolate (SA D22901), and two...

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Main Author:	Shien, Lee Lian
Format:	Thesis
Language:	English
Published:	2014
Subjects:	RC109-216 Infectious and parasitic diseases
Online Access:	http://eprints.usm.my/39510/1/Dr._Lee_Lian-24_pages.pdf
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id	my-usm-ep.39510
record_format	uketd_dc
spelling	my-usm-ep.395102019-04-12T05:25:58Z Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter 2014-11 Shien, Lee Lian RC109-216 Infectious and parasitic diseases Staphylococcus aureus is a major contributor of nosocomial infections of humans in the world. This study elucidates the genomic sequences of an MRSA (MRSA PR01) isolate from a patient with septicaemia in Kuala Lumpur, a clinical methicillinsusceptible S. aureus (MSSA) isolate (SA D22901), and two in vitro generated strains CR and COR which are derivatives of SA D22901 that developed resistance to antibiotics. CR and COR were isolated by exposing SA D22901 to become resistant to the antibiotics ciprofloxacin, and ciprofloxacin and oxacillin, respectively. These S. aureus strains were sequenced using a second generation sequencing platform. A combination of de novo and comparative assemblies, annotation and genome finishing was then applied to sequenced data to obtain the finished or draft genomes. The MRSA PR01 genome was sequenced to “noncontiguous- finished” status, whereas MSSA SA D22901 was sequenced to “improved high-quality draft” status and the derivatives CR and COR were assembled using reference mapping to MSSA D22901. MRSA PR01 has an extended antibiotic resistance pattern, and is resistant to many classes of antibiotics. Multi locus sequence typing analysis determined it to be of type ST239, a prevalent healthcare lineage across the world. SA D22901 contains a novel MLST profile, and is phylogenetically diverse from other S. aureus strains found in Malaysia. Genomic analysis of MRSA PR01 provides evidence of its adaptation to survive in a health care setting through acquisition of drug and antiseptic resistance genes encoded on mobile genetic elements, large chromosomal insertions and point mutations in housekeeping genes. Comparative analysis of the clinical MRSA and MSSA strains showed the importance of genes involved in cell wall synthesis in the acquisition of methicillin resistance. Variant analysis of the in vitro generated strains has uncovered mutations and mechanisms important in the evolution of ciprofloxacin and oxacillin resistance in S. aureus. Ciprofloxacin resistance was attained via mutations in two topoisomerase genes, while mutations in genes involved in cell wall synthesis and cell adhesion were found in the oxacillin-resistant COR strain. In conclusion, this study provided the whole genome sequences of several clinical and laboratory generated S. aureus strains and identified several key features that are involved in conferring antibiotic resistance. 2014-11 Thesis http://eprints.usm.my/39510/ http://eprints.usm.my/39510/1/Dr._Lee_Lian-24_pages.pdf application/pdf en public masters Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	RC109-216 Infectious and parasitic diseases
spellingShingle	RC109-216 Infectious and parasitic diseases Shien, Lee Lian Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter
description	Staphylococcus aureus is a major contributor of nosocomial infections of humans in the world. This study elucidates the genomic sequences of an MRSA (MRSA PR01) isolate from a patient with septicaemia in Kuala Lumpur, a clinical methicillinsusceptible S. aureus (MSSA) isolate (SA D22901), and two in vitro generated strains CR and COR which are derivatives of SA D22901 that developed resistance to antibiotics. CR and COR were isolated by exposing SA D22901 to become resistant to the antibiotics ciprofloxacin, and ciprofloxacin and oxacillin, respectively. These S. aureus strains were sequenced using a second generation sequencing platform. A combination of de novo and comparative assemblies, annotation and genome finishing was then applied to sequenced data to obtain the finished or draft genomes. The MRSA PR01 genome was sequenced to “noncontiguous- finished” status, whereas MSSA SA D22901 was sequenced to “improved high-quality draft” status and the derivatives CR and COR were assembled using reference mapping to MSSA D22901. MRSA PR01 has an extended antibiotic resistance pattern, and is resistant to many classes of antibiotics. Multi locus sequence typing analysis determined it to be of type ST239, a prevalent healthcare lineage across the world. SA D22901 contains a novel MLST profile, and is phylogenetically diverse from other S. aureus strains found in Malaysia. Genomic analysis of MRSA PR01 provides evidence of its adaptation to survive in a health care setting through acquisition of drug and antiseptic resistance genes encoded on mobile genetic elements, large chromosomal insertions and point mutations in housekeeping genes. Comparative analysis of the clinical MRSA and MSSA strains showed the importance of genes involved in cell wall synthesis in the acquisition of methicillin resistance. Variant analysis of the in vitro generated strains has uncovered mutations and mechanisms important in the evolution of ciprofloxacin and oxacillin resistance in S. aureus. Ciprofloxacin resistance was attained via mutations in two topoisomerase genes, while mutations in genes involved in cell wall synthesis and cell adhesion were found in the oxacillin-resistant COR strain. In conclusion, this study provided the whole genome sequences of several clinical and laboratory generated S. aureus strains and identified several key features that are involved in conferring antibiotic resistance.
format	Thesis
qualification_level	Master's degree
author	Shien, Lee Lian
author_facet	Shien, Lee Lian
author_sort	Shien, Lee Lian
title	Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter
title_short	Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter
title_full	Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter
title_fullStr	Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter
title_full_unstemmed	Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter
title_sort	comparative genomic of methicillinresistant staphylococcus aureus pr01 (mrsapr01) and methicillin-sensitive staphylococcus aureus sa d22901 (mssa sad22901) and methicillin resistant derivatives of the latter
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Perubatan
publishDate	2014
url	http://eprints.usm.my/39510/1/Dr._Lee_Lian-24_pages.pdf
_version_	1747820756924891136

Comparative genomic of methicillinresistant staphylococcus aureus PR01 (MRSAPR01) and methicillin-sensitive staphylococcus aureus SA D22901 (MSSA SAD22901) and methicillin resistant derivatives of the latter

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