James E. Bower

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.

An evaluation of the Xpert MTB/RIF assay and detection of false-positive rifampicin resistance in Mycobacterium tuberculosis.

Recent reports suggest that false-positive rifampicin resistance may be assigned by the Xpert MTB/RIF assay. We analysed 169 specimens using the MTB/RIF assay. Using culture as the gold standard, we found that the assay had 100% sensitivity and specificity for detecting M. tuberculosis. However, we found that the assay incorrectly assigned rifampicin resistance in 4/13 (31%) of cases.

Phylogenetic lineages of tuberculosis isolates in New Zealand and their association with patient demographics.

SETTING In New Zealand, the lineage genotypes of Mycobacterium tuberculosis clinical isolates and their role in the epidemiology of tuberculosis (TB) are currently unknown. OBJECTIVE 1) To measure the relative frequency of each phylogenetic lineage of the M. tuberculosis complex in New Zealand, and 2) to examine its relationship with patient demographics and multidrug-resistant TB (MDR-TB). METHODS All non-duplicate M. tuberculosis complex isolates recovered in 2010 and 2011 underwent large sequence polymorphism and/or single nucleotide polymorphism analyses. Mycobacterial interspersed repetitive units (MIRU) profiling was also performed for cluster identification. RESULTS New Zealand isolates were dominated by lineage 4 (Euro-American: 37.8%, 95%CI 33.6-42.2), followed by lineage 1 (Indo-Oceanic: 22.6%, 95%CI 19.1-26.5), lineage 2 (East Asian: 19.5%, 95%CI 16.2-23.3) and lineage 3 (East-African Indian, which included Central Asian: 17.7%, 95%CI 14.5-21.3). Lineage 2 accounted for 58.1% of MDR-TB cases from 2002 to 2011. Among immigrants, the predominant lineages corresponded to high prevalence lineages in the country of origin. In New Zealand-born individuals, Māori and NZ Europeans share the same predominant lineage, lineage 4, with a higher proportion of non-unique MIRU types observed in Māori cases. Lineage 3 was more prevalent in Māori than in NZ Europeans. CONCLUSION In New Zealand, M. tuberculosis complex phylogenetic lineage is associated with TB epidemiology in terms of ethnicity, country of origin and MDR-TB.

Comparative epidemiology of CTX-M-14 and CTX-M-15 producing Escherichia coli: Association with distinct demographic groups in the community in New Zealand

Extended spectrum beta-lactamase producing E. coli (ESBL-EC) are an emerging public health issue. In New Zealand (NZ), blaCTX-M-14 and blaCTX-M-15 are the most common ESBL genes. Although many studies describe risk factors for ESBL-EC, few describe risk factors for specific ESBL genes. Between January 2006 and December 2007, we characterized 108 consecutive, non-duplicate isolates of ESBL-EC at the Auckland Hospital laboratory. Demographic and clinical data were recorded. Of the 108, 54.6% (59) were CTX-M-15-EC, 26.9% (29) were CTX-M-14-EC and 12.09% were CTX-M-9 (13). The remaining seven isolates carried CTX-M-3 (3; 2.7%), CTX-M-65 (2; 1.8%), CTX-M-27 (1; 0.9%) and CTX-M-57 (1; 0.9%). CTX-M-15-EC were more likely than CTX-M-14-EC to be fluoroquinolone-resistant (86.4% versus 32.4%; p = 0.006) and to be non-susceptible to amoxicillin-clavulanate (84.7% versus 41.4%; p = 0.0001). Patients with CTX-M-15-EC were more likely to be of Indian ethnicity (34.5% versus 0%; p = 0.0012) and to have travelled recently (31.6% versus 4%; p = 0.0088). Patients with CTX-M-14-EC were more likely to have Chinese or South-East Asian ethnicity (48.1% versus 5.2%; p < 0.0001) and to have no history of either travel or prior hospital admission (44% versus 8.9%; p = 0.0006). These data imply that CTX-M-15 and CTX-M-14 producing E. coli are associated with distinct demographic subgroups in NZ.

High macrolide resistance in Mycoplasma genitalium strains causing infection in Auckland, New Zealand.

M ycoplasma genitalium has been implicated as a cause of acute and chronic nonchlamydial nongonococcal urethritis (NCNGU) and pelvic inflammatory disease (PID) ([1][1]). In New Zealand, as with many other countries, the preferred treatment for NCNGU is either azithromycin or doxycycline ([2][2]).

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.

Differential carriage of virulence-associated loci in the New Zealand Rangipo outbreak strain of Mycobacterium tuberculosis

Abstract Background: The Rangipo strain of Mycobacterium tuberculosis achieved notoriety in New Zealand due to its role in several tuberculosis (TB) outbreaks. Why this strain should be the source of relatively large clusters of the disease is unknown. In this work, we performed an in-depth analysis of the genome of the Rangipo strain to determine whether it offers clues to understanding its prevalence. Methods: Next-generation sequencing was performed on nine isolates which matched the Rangipo genotypic profile. Sequence reads were assembled against the H37Rv reference genome and single-locus variants identified. Unmapped reads were compared against the genome sequences of other M. tuberculosis strains, in particular CDC1551, Haarlem and Erdman. Results: Across the nine Rangipo strains, a total of 727 single-locus variants were identified with respect to H37Rv, of which 700 were common to all Rangipo strains sequenced. Within the common variants, 386 were non-synonymous, with 12 occurring in genes associated with M. tuberculosis virulence. Next-generation and Sanger sequencing determined the presence of three genes in the Rangipo isolates, which are absent in H37Rv, but which have been reported to be important for the pathogenicity of M. tuberculosis. The differentially encoded Rangipo genes consisted of transcriptional regulator EmbR2, and molybdopterin cofactor biosynthesis proteins A and B. The Rangipo strain also harbours an extended DNA helicase and an additional adenylate cyclase. Conclusions: Our study provides new insights into the genomic content of the New Zealand Rangipo strain of M. tuberculosis and highlights the presence of additional virulence-related loci not found in H37Rv.

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.

Rapid molecular diagnosis of the Mycobacterium tuberculosis Rangipo strain responsible for the largest recurring TB cluster in New Zealand

Despite New Zealand being a low-tuberculosis (TB) burden country, there are disproportionately high rates of TB in particular populations. Here, we report a rapid molecular diagnosis of the Mycobacterium tuberculosis Rangipo strain responsible for the largest recurring TB cluster in New Zealand.