European Society of Mycobacteriology - Instituto Nacional de Saúde ...

PP-34
PHYSIOLOGICAL FITNESS AND TRANSMISSION POTENTIAL OF MULTI-DRUG
RESISTANT Mycobacterium tuberculosis CLINICAL ISOLATES IN HONG KONG
CHAN Chiu Yeung Raphael 1 , CHAN Wai Chi Edward 1 , AU Tai Kong Mike 1 , LAI Wai Man Raymond 2 , YEW Wing Wai 3 ,
YIP Chi Wai 4 , KAM Kai Man 4 .
1 - Department of Microbiology, the Chinese University of Hong Kong;
2 - Department of Microbiology, Prince of Wales Hospital
3 - Tuberculosis & Chest Unit, Grantham Hospital,
4 - Tuberculosis Reference Laboratory, Department of Health, HKSAR, Hong Kong.
This study evaluated the infectivity and transmission potential of multi-drug resistant Mycobacterium tuberculosis (MDR-
MTB) strains by determining (i) whether resistance developed at a physiological cost which rendered them less capable
of surviving environmental stress and infecting human host, and (ii) the degree of genetic relatedness shared by resistant
organisms, which indicated the extent by which they spread among humans. The relative growth rates of selected isolates
were measured using the MGIT system and compared to that of drug-sensitive strains. Our data showed that their average
initial growth rate, measured within 7 days of inoculation, was inversely proportional to the number of mutations
they harbored in key resistance genes, with strains carrying 5 mutations growing at a rate 46% slower than that of the
wild type. These findings suggested that resistance gene mutations in MTB imposed a range of physiological cost characterized
by reduced growth fitness. However, results of epidemiological typing showed that 34% of the 402 MDR-MTB
isolates analyzed exhibited genetic relationship to other strains, indicating that such fitness cost did not significantly affect
the ability of MDR-MTB to transmit between human hosts and cause infection. Importantly, the identification of five major
clusters of 50 strains strongly suggests that infection due to dissemination of ‘parental’ MDR-MTB clones is common.
On the other hand, the majority of test strains displayed a unique genetic profile, indicating that MDR-MTB might also
emerge independently through drug selection within individual patient. The DNA fingerprints and growth fitness data of
local resistant isolates may be used for matching the genetic identities, predicting transmission potential, and tracing the
routes of dissemination of future MDR-MTB isolates in the community.
This work was supported by the Research Fund for the Control of Infectious Diseases (Project code 6902191 and 6902200)
106 ESM 2009