Association of ISMav6 with the Pattern of Antibiotic Resistance in Korean Mycobacterium avium Clinical Isolates but No Relevance between Their Genotypes and Clinical Features

Abstract

The aim of this study was to genetically characterize clinical isolates from patients diagnosed with Mycobacterium avium lung disease and to investigate the clinical significance. Multi-locus sequencing analysis (MLSA) and pattern of insertion sequence analysis of M. avium isolates from 92 Korean patients revealed that all isolates were M. avium subspecies hominissuis. In hsp65 sequevar analysis, codes 2, 15, and 16 were most frequently found (88/92) with similar proportions among cases additionally two isolates belonging to code N2 and an unreported code were identified, respectively. In insertion element analysis, all isolates were IS1311 positive and IS900 negative. Four of the M. avium subsp. hominissuis isolates did not harbor IS1245 and 1 of the M. avium isolates intriguingly harbored DT1, which is thought to be a M. intracellulare-specific element. M. avium subsp. hominissuis harboring ISMav6 is prevalent in Korea. No significant association between clinical manifestation and treatment response has been found in patients with the hsp65 code type and ISMav6, indicating that no specific strain/genotype among M. avium subsp. hominissuis organisms was a major source of M. avium lung disease. Interestingly, the presence of ISMav6 was correlated with greater resistance to moxifloxacin. Conclusively, the genotype of Korean M. avium subsp. hominissuis isolates is not a disease determinant responsible for lung disease and specific virulent factors of M. avium subsp. hominissuis need to be investigated further.

Molecular Characterization of Mycobacterium avium subsp. hominissuis of Two Groups of Lymph Nodes, Being Intradermal Tuberculin or Interferon-Gamma Test Positive and Negative, Isolated from Swiss Cattle at Slaughter

“…IS Mav6 , a homologous insertion sequence to the original bird-type IS 901 with 95% sequence identity ( 8 ), was found in two MAH isolates comprising hsp65 sequevar code 15. This combination of IS Mav6 together with hsp65 sequevar code 15 has been described for Japanese clinical isolates often recovered from sputum ( 8 , 37 ) and more recently from Korean clinical isolates, where a high prevalence of IS Mav6 was observed ( 38 ). Adachi et al compared IS Mav6 in human and swine isolates detecting IS Mav6 in human samples only ( 39 ).…”

Retrospective evaluation of natural course in mild cases of Mycobacterium avium complex pulmonary disease

“…Several investigators have identified various bacterial factors related to deterioration of mycobacteriosis [11, 17, 28, 29]. The prevalence of IS Mav6 is reported to be significantly higher in the genome of pathogenic MAC strains in the Japanese and Korean populations [30, 31]. However, we found no significant difference in the prevalence of IS Mav6 or IS Mav6 in cfp29 between the treatment and observation groups, and disease severity did not appear to be dependent on pathophysiology related to IS Mav6 in cfp29 .…”

Genotyping and clarithromycin susceptibility testing of Mycobacterium avium subsp. hominissuis isolated in Tuscany, Italy

“…No association of a specific VNTR pattern with a particular clinical feature, such as the pulmonary or lymph node infection, was observed. Further studies will provide information about possible association between MAH genotypes and other clinical characteristics in our geographical region; about this, other studies report that in Japan M. avium genotypes were associated with disease progression or therapeutic response (Kikuchi et al, 2009;Kikuchi et al, 2014), or that there was no significant association between MAH genotypes isolated from Korean patients and clinical manifestation or treatment response (Kim et al, 2016;Kim et al, 2012;Tatano et al, 2012).…”