Chapter 16 : Of Bacteria and Bile

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Of Bacteria and Bile, Page 1 of 2

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The antibacterial activities of bile salts include detergent activity on cell membranes, protein denaturation, and DNA damage. However, many bacterial species are resistant to the antibacterial activity of bile salts. Bile salts may thus be viewed both as antibacterial compounds and as signals used by bacteria to identify bile-containing animal environments. This chapter reviews the mechanisms employed by , , and other intestinal bacteria to respond to bile salts, with emphasis on their relevance for pathogenesis. The reader is also referred to two comprehensive, insightful reviews on bacterial responses to bile. Unconjugated forms of bile salts are amphipatic molecules that can enter the bacterial cell by crossing membrane bilayers. Furthermore, in the outer membrane of gram-negative bacteria, porins provide passage to both unconjugated and conjugated bile salts. Bile salts, especially if unconjugated, may easily reach the bacterial ctyoplasm by diffusion. Bile salts may also bind to specific receptors in the bacterial surface, activating signal transduction pathways that change gene expression patterns. Bile extract or individual bile salts can be added to microbiological media, thus permitting reductionist studies of bacterial bile resistance in the laboratory. It is hypothesized that nonmutational, reversible resistance may involve stochastic activation of one or more efflux systems that transport bile outside the cell.

Citation: Casadesús J, Hernández S, Cota I, Ramos-Morales F. 2011. Of Bacteria and Bile, p 153-162. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch16

Key Concept Ranking

Gene Expression and Regulation
Base Excision Repair
Nucleotide Excision Repair
Integral Membrane Proteins
Outer Membrane Proteins
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Image of FIGURE 1

Bile salts can enter the bacterial cell either by diffusion or by passage through outer membrane pores, and subsequent diffusion through the cytoplasmic membrane. Bile salt influx is reduced by envelope structures such as LPS and ECA. Certain envelope alterations (e.g., LPS or ECA defects, reduced association of Braun lipoprotein to peptidoglycan) cause bile sensitivity, whereas others (e.g., lack of AsmA protein in the outer membrane) increase bile resistance.

Citation: Casadesús J, Hernández S, Cota I, Ramos-Morales F. 2011. Of Bacteria and Bile, p 153-162. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch16
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Image of FIGURE 2

Model for bile-induced DNA damage and subsequent repair of bile-induced DNA lesions, based on studies with Primary lesions (perhaps oxidized cytosines) may be directly caused by bile salts or by reactive oxygen species generated in the presence of bile salts. Primary lesions are repaired by Dam-directed mismatch repair and by BER. Either process generates single-stranded DNA intermediates that can induce the SOS response. Direct SOS induction can also occur if bile-induced primary lesions impair DNA replication. Single-strand breaks generated by DNA repair can give rise to double-strand breaks upon DNA replication. SOS induction may permit translesion DNA replication by the DinB polymerase, thus helping to overcome DNA replication blockage. In turn, RecBCD may rescue arrested replication forks by either degradation of double-stranded DNA ends or recombinational repair.

Citation: Casadesús J, Hernández S, Cota I, Ramos-Morales F. 2011. Of Bacteria and Bile, p 153-162. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch16
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Image of FIGURE 3

Simplified diagrams of two screens for genetic analysis of bile resistance in using Roth’s T-POP transposon. An additional screen, not included in the diagram, can select isolates with increased resistance to bile. Such a screen is analogous to the search for suppressors, except that the selective agar plates contain a concentration of bile above the wild-type MIC.

Citation: Casadesús J, Hernández S, Cota I, Ramos-Morales F. 2011. Of Bacteria and Bile, p 153-162. In Maloy S, Hughes K, Casadesús J (ed), The Lure of Bacterial Genetics. ASM Press, Washington, DC. doi: 10.1128/9781555816810.ch16
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