The human body is covered in bacteria. These bacteria are broadly categorized as being either commensal (helpful) or pathogenic (harmful). The truth is that many types of bacteria can either be helpful or harmful depending on cues they receive from their local environment. Moreover, the environment can also influence whether a bacterial infection is rapid (acute) or long-term (chronic). For example, Pseudomonas aeruginosa bacteria cause acute infections in patients with pneumonia, as well as chronic infections in patients with cystic fibrosis. Other types of bacteria including Staphylococcus aureus, Escherichia coli, and different species of Streptococcus can also cause both acute and chronic infections.
Chronic bacterial infections are often poorly understood. It is generally thought that chronic bacterial infections begin when bacteria use special disease-causing proteins called virulence factors to establish a stronghold within the host. Next, the bacteria create biofilms (think bunkers) that are matrix-enclosed communities of bacteria that resist killing by antibiotics. This model may seem convincing, but conclusive studies have not yet been done. A recent study by Morgan et al. provided new insight into chronic infection by describing the roles of virulence factors and biofilms in chronic infection.
The group first studied patient isolates from seven chronic wounds and observed that several virulence factors and biofilm functions in P. aeruginosa were inactive, challenging current chronic-infection dogma. To investigate how these bacteria establish chronic infection, they used a technique called Tn-seq, which uses mobile segments of DNA called transposons. Transposons can ‘hop’ around a genome by excising themselves from their current location and inserting themselves elsewhere on the genome. When a transposon inserts itself into a gene, it can often disrupt gene function. If the targeted gene plays an important role in chronic infection, then the gene disruption should prevent chronic infection. The location of the transposon, and the gene in question, can then be identified by DNA sequencing. Using this technique, the scientists identified a large number of genes that when disrupted significantly impaired P. aeruginosa’s ability to cause chronic infection. Some of the important genes identified were involved in bacterial growth, metabolism, and structure. Next, using three different experimental designs they observed that functions that reduce stress associated with high-density bacterial growth (i.e. lack of oxygen, bacterial membrane disruption) were critical for chronic infection.
The results from this study not only update the model for bacterial chronic infection, but also suggest that current therapeutics, which target biofilm formation and virulence factors, may not be very effective. Morgan et al. suggest in the conclusion of their article that their experimental design could be an effective tool for screening new classes of antibiotics.
Summary written by: Emma Finlayson-Trick
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Bacterial fitness in chronic wounds appears to be mediated by the capacity for high-density growth, not virulence or biofilm functions
Sarah J. Morgan, Soyeon I. Lippman, Gilbert E. Bautista, Joe J. Harrison, Christopher L. Harding, Larry A. Gallagher, Ann-Chee Cheng, Richard Siehnel, Sumedha Ravishankar, Marcia L. Usui, John E. Olerud, Philip Fleckman, Randall D. Wolcott, Colin Manoil, Pradeep K. Singh