Mycobacteria use protein to create diverse populations, avoid drugs
Eric J. Rubin and E. Hesper Rego
Eric J. Rubin, M.D., Ph.D., of Harvard T.H. Chan School of Public Health, and E. Hesper Rego, Ph.D., of Yale University School of Medicine, and their coworkers first studied Mycobacterium smegmatis, a close relative of Mycobacterium tuberculosis (Mtb), the microbe that causes TB. Using fluorescent reporter molecules and time-lapse microscopy, they examined individual cells as they grew and divided. Mycobacteria can generate daughter cells through asymmetric growth, resulting in genetically identical, but physiologically diverse, populations. The mechanisms underlying this ability and the extent to which the cells' size, growth rate and other physiological properties relate to survival in mycobacterial populations were not well understood.
Dr. Rubin and colleagues determined that the protein product of a single gene, lamA, is a member of the protein machinery that is active when mycobacteria divide. The protein--which is not known to exist in other rod-shaped bacteria or other organisms--seems to allow for asymmetrical growth in new mycobacterial cells made during cell division. The asymmetrical growth leads to bacteria with wide variations in physiological properties and susceptibility to antibiotics.
In experiments using Mtb, the scientists found that mycobacteria without lamA formed far less diverse bacteria with more uniform susceptibility to antibiotics. When exposed to the front-line TB drug rifampicin, for example, Mtb cells lacking lamA were less able to survive than wildtype bacteria. In the future, it may be possible to devise ways to inhibit lamA or its protein. This could lead to reduced variation in Mtb populations and, potentially, to more uniform vulnerability to drugs, according to the scientists.
Original publication
Other news from the department science
Get the life science industry in your inbox
From now on, don't miss a thing: Our newsletter for biotechnology, pharma and life sciences brings you up to date every Tuesday and Thursday. The latest industry news, product highlights and innovations - compact and easy to understand in your inbox. Researched by us so you don't have to.