Micheál Mac Aogáin

Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.

Detailed characterization of the first high-level azithromycin-resistant Neisseria gonorrhoeae cases in Ireland

Detailed characterization of the first high-level azithromycin-resistant Neisseria gonorrhoeae cases in Ireland

Draft Genome Sequences of Three Mycobacterium chimaera Respiratory Isolates

ABSTRACT Mycobacterium chimaera is an opportunistic human pathogen implicated in both pulmonary and cardiovascular infections. Here, we report the draft genome sequences of three strains isolated from human respiratory specimens.

Enhanced Tracking of Nosocomial Transmission of Endemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Type IV Isolates among Patients and Environmental Sites by Use of Whole-Genome Sequencing

ABSTRACT Whole-genome sequencing (WGS) of 41 patient and environmental sequence type 22 methicillin-resistant Staphylococcus aureus staphylococcal cassette chromosome mec type IV (ST22-MRSA-IV) isolates recovered over 6 weeks in one acute hospital ward in Dublin, Ireland, where ST22-MRSA IV is endemic, revealed 228 pairwise combinations differing by <40 single nucleotide variants corresponding to potential cross-transmission events (CTEs). In contrast, 15 pairwise combinations of isolates representing five CTEs were previously identified by conventional molecular epidemiological typing. WGS enhanced ST22-MRSA-IV tracking and highlighted potential transmission of MRSA via the hospital environment.

Identification of a novel mutation at the primary dimer interface of GyrA conferring fluoroquinolone resistance in Clostridium difficile

The aim of this study was to determine whether alternative resistance mechanisms, other than mutation in the quinolone resistance-determining region (QRDR) of DNA gyrase, could confer fluoroquinolone resistance in Clostridium difficile. An in vitro-generated C. difficile mutant exhibiting increased fluoroquinolone resistance was isolated through antibiotic selection on ciprofloxacin. The QRDR of this mutant was investigated by chain-termination sequencing and was found to be devoid of mutation. To determine the nature of the non-QRDR resistance mechanism in this strain, the genomes of the mutant and wild-type strains were sequenced. The gyrBA region from a collection of clinical isolates exhibiting variable fluoroquinolone resistance levels was also sequenced and was compared with that present in 918 publicly available C. difficile genomic data sets. Whole-genome sequence analysis of the fluoroquinolone-resistant mutant revealed a single non-synonymous substitution (Ala384Asp) at the predicted primary dimer interface of GyrA, far beyond the classically defined QRDR. This novel mutation caused increased resistance to ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin while conferring hypersusceptibility to novobiocin. Several novel extra-QRDR polymorphisms in C. difficile DNA gyrase were identified among clinical isolates, whilst observed fluoroquinolone resistance in strains devoid of gyrBA mutations confirmed the existence of DNA gyrase-independent resistance mechanisms in this species. In conclusion, we report the first non-QRDR mutation to confer fluoroquinolone resistance in C. difficile. Although the Ala384Asp substitution was not detected in clinical isolates, this study revealed a diversity of alternative extra-QRDR polymorphisms in DNA gyrase whose association with fluoroquinolone resistance warrants further investigation.

Draft Genome Sequence of a Multidrug-Resistant New Zealand Isolate of Mycobacterium tuberculosis Lineage 3.

ABSTRACT Multidrug resistance constitutes a threat worldwide to the management of tuberculosis (TB). We report the draft whole-genome sequence of a lineage 3 (East-African Indian) isolate of Mycobacterium tuberculosis which presented as multidrug resistant in New Zealand, and describe a number of single-nucleotide polymorphisms in genes relating to drug resistance.

Fourteen Draft Genome Sequences for the First Reported Cases of Azithromycin-Resistant Neisseria gonorrhoeae in Ireland

ABSTRACT Here, we report the draft genome assemblies of 14 azithromycin-resistant Neisseria gonorrhoeae clinical isolates, representing the first such strains identified in Ireland. Among these isolates are the first reported highly resistant strains (MIC >256 mg/liter), which both belonged to the ST1580 sequence type.

Typhlocolitis associated with Clostridium difficile ribotypes 078 and 110 in neonatal piglets from a commercial Irish pig herd

BackgroundClostridium difficile is a recognised cause of typhlocolitis and diarrhoea in neonatal pigs but has never been confirmed in association with pathology and disease in Irish pigs.Case PresentationFour neonatal piglets, with a history of diarrhoea were referred to the Central Veterinary Research Laboratory, Backweston for necropsy. They were from a fully integrated, commercial pig farm with approximately 1000 sows. Three piglets had acute, superficial, erosive and suppurative typhlocolitis and the other had mild suppurative mesocolitis. Clostridium difficile (C. difficile) toxins A/B were detected using ELISA in the colonic contents from each piglet. C. difficile isolates from two of the piglets were PCR-ribotyped as 078 and an isolate from a third pig was ribotyped as 110.ConclusionsThis is the first report confirming C. difficile in association with typhlocolitis in Irish pigs.

Draft Genome Sequence of a New Zealand Rangipo Strain of Mycobacterium tuberculosis

ABSTRACT The Rangipo genotype of the Mycobacterium tuberculosis complex has been associated with a number of tuberculosis (TB) outbreaks in New Zealand. We report here the draft whole-genome sequence of a representative isolate of this strain.

Draft Genome Sequence of a Drug-Susceptible New Zealand Isolate of Mycobacterium tuberculosis Lineage 3

ABSTRACT We report here the draft whole-genome sequence of a drug-susceptible lineage 3 (East-African Indian) isolate of Mycobacterium tuberculosis from New Zealand (NZ3DS1) and compare it to a multidrug-resistant lineage 3 isolate (NZ3MDR1) with an identical 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat profile.