<p><i>Mycobacterium abscessus</i> is
an emerging infectious pathogen capable of causing pulmonary disease similar to
tuberculosis, but has many intrinsic and extrinsic properties making it more
drug-resistant than <i>Mycobacterium tuberculosis</i>. Current treatments,
including those used for <i>M. tuberculosis</i> infection, have had poor
results. Although <i>in vitro</i> studies
have shown promise with drug treatment for this microorganism, clinical trials
have been mostly unsuccessful. An <i>in
vitro </i>model that mimics the physiological stresses encountered within the
human body is likely to enable the discovery of mechanisms of antibiotic
resistance used by <i>M. abscessus</i>
during infection. Therefore, we subjected <i>M. abscessus</i> to a combination
of stresses thought to be encountered by mycobacteria inside the human body. We
subjected the pathogen to low oxygen, low pH, and nutrient starvation. This is
the first report on subjecting <i>M. abscessus</i> to such a combination of
stresses. It is also the first to investigate the effect of the combination of
stresses on the tolerance of the pathogen to antibiotics, and the effect of
efflux pump inhibitors under such conditions. We found that under these
conditions, <i>M. abscessus</i> entered a non-replicating state. We
investigated whether the multiple-stressed <i>M.
abscessus</i> displayed altered tolerance to antibiotics commonly used to treat
infection, and whether efflux pump inhibitors affected the antibiotic
resistance under such conditions.<i> </i>We
found that when subjected to our multiple stress model, <i>M. abscessus</i> in
the reactivating phase had higher tolerance to erythromycin in combination with
efflux pump inhibitors verapamil and reserpine compared to non-replicating <i>M.
abscessus</i>. Reactivating phase cells had a higher tolerance to antibiotic
erythromycin than non-replicating cells. Reactivating phase cells also showed
antibiotic tolerance in the presence of ATP. This physiologically-relevant
experimental model for <i>M. abscessus</i>
could potentially be used in discovering the mechanisms of antibiotic
resistance in the pathogen.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/12249764 |
| Date | 05 May 2020 |
| Creators | Andrea M Funk (8800892) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/MICROBIOLOGICAL_STUDIES_ON_THE_ANTIBIOTIC_TOLERANCE_OF_NON-REPLICATING_MYCOBACTERIUM_ABSCESSUS_EFFECTS_OF_EFFLUX_PUMP_INHIBITORS_AND_METABOLIC_ENERGY_SOURCES/12249764 |
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