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1.
Clin Microbiol Rev ; : e0012123, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38466110

ABSTRACT

SUMMARYEnterococci are a diverse group of Gram-positive bacteria that are typically found as commensals in humans, animals, and the environment. Occasionally, they may cause clinically relevant diseases such as endocarditis, septicemia, urinary tract infections, and wound infections. The majority of clinical infections in humans are caused by two species: Enterococcus faecium and Enterococcus faecalis. However, there is an increasing number of clinical infections caused by non-faecium non-faecalis (NFF) enterococci. Although NFF enterococcal species are often overlooked, studies have shown that they may harbor antimicrobial resistance (AMR) genes and virulence factors that are found in E. faecium and E. faecalis. In this review, we present an overview of the NFF enterococci with a particular focus on human clinical manifestations, epidemiology, virulence genes, and AMR genes.

3.
Int J Mol Sci ; 24(23)2023 Nov 22.
Article in English | MEDLINE | ID: mdl-38068949

ABSTRACT

The structure and function of infant skin is not fully developed until 34 weeks of gestation, and this immaturity is associated with risk of late-onset sepsis (LOS). Topical coconut oil improves preterm-infant skin integrity and may reduce LOS. However, data on early-life skin-microbiome succession and potential effects of emollient skin care in preterm infants are scarce. We therefore collected skin-microbiome samples from the ear, axilla, and groin on days 1, 7, 14, and 21 from preterm infants born <30 weeks of gestation as part of a randomized clinical trial of standard skin care vs. topical coconut oil. We found that within-sample microbiome diversity was highest on day 1 after birth, with a subsequent decline and emergence of Staphylococcus genus dominance from day 7. Moreover, microbiome assembly was less diverse in infants receiving coconut oil vs. standard skin care. Our study provides novel data on preterm-infant skin-microbiome composition and highlights the modifying potential of emollient skin care.


Subject(s)
Microbiota , Sepsis , Infant , Infant, Newborn , Humans , Infant, Premature , Coconut Oil/pharmacology , Emollients/pharmacology , Skin
4.
Microb Genom ; 9(12)2023 Dec.
Article in English | MEDLINE | ID: mdl-38117559

ABSTRACT

In 2010 a single isolate of a trimethoprim-resistant multilocus sequence type 5, Panton-Valentine leucocidin-positive, community-associated methicillin-resistant Staphylococcus aureus (PVL-positive ST5 CA-MRSA), colloquially named WA121, was identified in northern Western Australia (WA). WA121 now accounts for ~14 % of all WA MRSA infections. To gain an understanding of the genetic composition and phylogenomic structure of WA121 isolates we sequenced the genomes of 155 WA121 isolates collected 2010-2021 and present a detailed genomic description. WA121 was revealed to be a single clonally expanding lineage clearly distinct from sequenced ST5 strains reported outside Australia. WA121 strains were typified by the presence of the distinct PVL phage φSa2wa-st5, the recently described methicillin resistance element SCCmecIVo carrying the trimethoprim resistance (dfrG) transposon Tn4791, the novel ß-lactamase transposon Tn7702 and the epidermal cell differentiation inhibitor (EDIN-A) plasmid p2010-15611-2. We present evidence that SCCmecIVo together with Tn4791 has horizontally transferred to Staphylococcus argenteus and evidence of intragenomic movement of both Tn4791 and Tn7702. We experimentally demonstrate that p2010-15611-2 is capable of horizontal transfer by conjugative mobilization from one of several WA121 isolates also harbouring a pWBG749-like conjugative plasmid. In summary, WA121 is a distinct and clonally expanding Australian PVL-positive CA-MRSA lineage that is increasingly responsible for infections in indigenous communities in northern and western Australia. WA121 harbours a unique complement of mobile genetic elements and is capable of transferring antimicrobial resistance and virulence determinants to other staphylococci.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Methicillin-Resistant Staphylococcus aureus/genetics , Australia , Leukocidins/genetics , Genomics , Western Australia
5.
Microb Genom ; 7(10)2021 10.
Article in English | MEDLINE | ID: mdl-34704920

ABSTRACT

Neisseria meningitidis, the meningococcus, resides exclusively in humans and causes invasive meningococcal disease (IMD). The population of N. meningitidis is structured into stable clonal complexes by limited horizontal recombination in this naturally transformable species. N. meningitidis is an opportunistic pathogen, with some clonal complexes, such as cc53, effectively acting as commensal colonizers, while other genetic lineages, such as cc11, are rarely colonizers but are over-represented in IMD and are termed hypervirulent. This study examined theoretical evolutionary pathways for pathogenic and commensal lineages by examining the prevalence of horizontally acquired genomic islands (GIs) and loss-of-function (LOF) mutations. Using a collection of 4850 genomes from the BIGSdb database, we identified 82 GIs in the pan-genome of 11 lineages (10 hypervirulent and one commensal lineage). A new computational tool, Phaser, was used to identify frameshift mutations, which were examined for statistically significant association with genetic lineage. Phaser identified a total of 144 frameshift loci of which 105 were shown to have a statistically significant non-random distribution in phase status. The 82 GIs, but not the LOF loci, were associated with genetic lineage and invasiveness using the disease carriage ratio metric. These observations have been integrated into a new model that infers the early events of the evolution of the human adapted meningococcus. These pathways are enriched for GIs that are involved in modulating attachment to the host, growth rate, iron uptake and toxin expression which are proposed to increase competition within the meningococcal population for the limited environmental niche of the human nasopharynx. We surmise that competition for the host mucosal surface with the nasopharyngeal microbiome has led to the selection of isolates with traits that enable access to cell types (non-phagocytic and phagocytic) in the submucosal tissues leading to an increased risk for IMD.


Subject(s)
Bacterial Proteins/genetics , Meningococcal Infections/microbiology , Neisseria meningitidis/pathogenicity , Whole Genome Sequencing/methods , Evolution, Molecular , Frameshift Mutation , Gene Transfer, Horizontal , Genome, Bacterial , Genomic Islands , Humans , Loss of Function Mutation , Nasopharynx/microbiology , Neisseria meningitidis/genetics , Symbiosis , Virulence
6.
Antibiotics (Basel) ; 10(2)2021 Jan 21.
Article in English | MEDLINE | ID: mdl-33494538

ABSTRACT

While antimicrobial resistance (AMR) is seen in both Neisseria gonorrhoeae and Neisseria meningitidis, the former has become resistant to commonly available over-the-counter antibiotic treatments. It is imperative then to develop new therapies that combat current AMR isolates whilst also circumventing the pathways leading to the development of AMR. This review highlights the growing research interest in developing anti-virulence therapies (AVTs) which are directed towards inhibiting virulence factors to prevent infection. By targeting virulence factors that are not essential for gonococcal survival, it is hypothesized that this will impart a smaller selective pressure for the emergence of resistance in the pathogen and in the microbiome, thus avoiding AMR development to the anti-infective. This review summates the current basis of numerous anti-virulence strategies being explored for N. gonorrhoeae.

7.
PLoS One ; 12(10): e0186839, 2017.
Article in English | MEDLINE | ID: mdl-29065137

ABSTRACT

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD). A recombinant vaccine called Bexsero® incorporates four subcapsular antigens (fHbp, NHBA, NadA and PorA) which are used to assign a Bexsero® antigen sequence type (BAST) to each meningococcal strain. The vaccine elicits an immune response against combinations of variants of these antigens which have been grouped into specific BAST profiles that have been shown to have different distributions within geographical locations thus potentially affecting the efficacy of the vaccine. In this study, invasive meningococcal disease isolates from the western seaboard of Australia (Western Australia; WA) were compared to those from the south-eastern seaboard (Victoria; VIC) from 2008 to 2012. Whole-genome sequencing (WGS) of 131 meningococci from VIC and 70 meningococci from WA were analysed for MLST, FetA and BAST profiling. Serogroup B predominated in both jurisdictions and a total of 10 MLST clonal complexes (cc) were shared by both states. Isolates belonging to cc22, cc103 and cc1157 were unique to VIC whilst isolates from cc60 and cc212 were unique to WA. Clonal complex 41/44 represented one-third of the meningococcal population in each state but the predominant ST was locally different: ST-6058 in VIC and ST-146 in WA. Of the 108 BAST profiles identified in this collection, only 9 BASTs were simultaneously observed in both states. A significantly larger proportion of isolates in VIC harboured alleles for the NHBA-2 peptide and fHbp-1, antigenic variants predicted to be covered by the Bexsero® vaccine. The estimate for vaccine coverage in WA (47.1% [95% CI: 41.1-53.1%]) was significantly lower than that in VIC (66.4% [95% CI: 62.3-70.5%]). In conclusion, the antigenic structure of meningococci causing invasive disease in two geographically distinct states of Australia differed significantly during the study period which may affect vaccine effectiveness and highlights the need for representative surveillance when predicting potential impact of meningococcal B vaccines.


Subject(s)
Neisseria meningitidis/classification , Antigens, Bacterial/immunology , Genes, Bacterial , Humans , Neisseria meningitidis/genetics , Neisseria meningitidis/immunology , Victoria , Western Australia
8.
Sci Rep ; 7: 44442, 2017 03 14.
Article in English | MEDLINE | ID: mdl-28290510

ABSTRACT

Pathogenic meningococci have acquired a 24 kb capsule synthesis island (cps) by horizontal gene transfer which consists of a synthetic locus and associated capsule transport genes flanked by repetitive Regions D and D'. Regions D and D' contain an intact gene encoding a UDP-galactose epimerase (galE1) and a truncated remnant (galE2), respectively. In this study, GalE protein alleles were shown to be either mono-functional, synthesising UDP-galactose (UDP-Gal), or bi-functional, synthesising UDP-Gal and UDP-galactosamine (UDP-GalNAc). Meningococci possessing a capsule null locus (cnl) typically possessed a single bi-functional galE. Separation of functionality between galE1 and galE2 alleles in meningococcal isolates was retained for all serogroups except serogroup E which has a synthetic requirement for UDP-GalNAc. The truncated galE2 remnant in Region D' was also phylogenetically related to the bi-functional galE of the cnl locus suggesting common ancestry. A model is proposed in which the illegitimate recombination of the cps island into the galE allele of the cnl locus results in the formation of Region D' containing the truncated galE2 locus and the capture of the cps island en bloc. The retention of the duplicated Regions D and D' enables inversion of the synthetic locus within the cps island during bacterial growth.


Subject(s)
Gene Transfer, Horizontal/genetics , Meningitis, Meningococcal/genetics , Neisseria meningitidis/genetics , UDPglucose 4-Epimerase/genetics , Bacterial Capsules/genetics , Humans , Meningitis, Meningococcal/microbiology , Neisseria meningitidis/pathogenicity , Repetitive Sequences, Nucleic Acid/genetics , Uridine Diphosphate Galactose/biosynthesis
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