Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia
Abstract Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear.We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR-MTBC strains from Karakalpakstan, Uzbekistan (2001-2006).One MTBC-clone (termed Central Asian outbreak, CAO) with resistance mediating mutations to eight anti-TB drugs existed prior the worldwide introduction of standardized WHO-endorsed directly observed treatment, short-course (DOTS). DOTS implementation in Karakalpakstan in 1998 likely selected for these CAO-strains, comprising 75% of sampled MDR-TB strains in 2005/2006. CAO-strains were also identified in a previously published cohort from Samara, Russia (2008-2010). Similarly, transmission success and resistance development was linked to mutations compensating fitness deficits associated with rifampicin resistance.The genetic make-up of these outbreak clades threatens the success of both empirical and standardized guideline driven MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
bioRxiv.org - (2020) vom: 18. Jan. Zur Gesamtaufnahme - year:2020 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Merker, Matthias [VerfasserIn] |
|---|
| Links: |
|---|
| doi: |
10.1101/334599 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI000289426 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI000289426 | ||
| 003 | DE-627 | ||
| 005 | 20230429100145.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200312s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/334599 |2 doi | |
| 035 | |a (DE-627)XBI000289426 | ||
| 035 | |a (DE-599)biorXiv10.1101/334599 | ||
| 035 | |a (biorXiv)10.1101/334599 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 570 |q DE-84 | |
| 100 | 1 | |a Merker, Matthias |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear.We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR-MTBC strains from Karakalpakstan, Uzbekistan (2001-2006).One MTBC-clone (termed Central Asian outbreak, CAO) with resistance mediating mutations to eight anti-TB drugs existed prior the worldwide introduction of standardized WHO-endorsed directly observed treatment, short-course (DOTS). DOTS implementation in Karakalpakstan in 1998 likely selected for these CAO-strains, comprising 75% of sampled MDR-TB strains in 2005/2006. CAO-strains were also identified in a previously published cohort from Samara, Russia (2008-2010). Similarly, transmission success and resistance development was linked to mutations compensating fitness deficits associated with rifampicin resistance.The genetic make-up of these outbreak clades threatens the success of both empirical and standardized guideline driven MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan. | ||
| 700 | 1 | |a Barbier, Maxime |e verfasserin |4 aut | |
| 700 | 1 | |a Cox, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Rasigade, Jean-Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Feuerriegel, Silke |e verfasserin |4 aut | |
| 700 | 1 | |a Kohl, Thomas A. |e verfasserin |4 aut | |
| 700 | 1 | |a Diel, Roland |e verfasserin |4 aut | |
| 700 | 1 | |a Borrell, Sonia |e verfasserin |4 aut | |
| 700 | 1 | |a Gagneux, Sebastien |e verfasserin |4 aut | |
| 700 | 1 | |a Nikolayevskyy, Vladyslav |e verfasserin |4 aut | |
| 700 | 1 | |a Andres, Sönke |e verfasserin |4 aut | |
| 700 | 1 | |a Nübel, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Supply, Philip |e verfasserin |4 aut | |
| 700 | 1 | |a Wirth, Thierry |e verfasserin |4 aut | |
| 700 | 1 | |a Niemann, Stefan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2020) vom: 18. Jan. |
| 773 | 1 | 8 | |g year:2020 |g day:18 |g month:01 |
| 856 | 4 | 0 | |u https://doi.org/10.7554/elife.38200 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/334599 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2020 |b 18 |c 01 | ||
| 953 | |2 045F |a 570 | ||