Regulation of Bacterial Virulence

Many pathogenic bacteria are capable of living either outside or inside a host and of attacking a variety of host species. Proliferation in these differing environments demands an efficient regulation of virulence, the aim being to have virulence factors available as required. Four different regulatory mechanisms have been described:

■ DNA changes. The nucleotide sequences of virulence determinants are changed. Examples of this include pilin gene variability involving intracellu-lar recombination as described above in gonococci and inverting a leader sequence to switch genes on and off in the phase variations of H antigens in salmonellae (see p. 284).

■ Transcriptional regulation. The principle of transcriptional control of virulence determinants is essentially the same as that applying to the regulation of metabolic genes, namely repression and activation (see p. 169f.): — Simple regulation. Regulation of the diphtheria toxin gene has been thoroughly researched. A specific concentration of iron in the cytoplasm activates the diphtheria toxin regulator (DtxR). The resulting active repres-sor prevents transcription of the toxin gene by binding to the promoter region. Other virulence genes can also be activated by regulators using this mechanism.

— Complex regulation, virulence regulon. In many cases, several virulence genes are switched on and off by the same regulator protein. The virulence determinants involved are either components of the same operon or are located at different genome sites. Several vir (virulence) genes with promoter regions that respond to the same regulator protein form a so-called vir regulon. Regulation of the virulence regulon of Bordetella pertussis by means of gene activation is a case in point that has been studied in great detail. This particular regulon comprises over 20 virulence determinants, all controlled by the same vir regulator protein (or BvgA coding region) (Fig. 1.4).

■ Posttranscriptional regulation. This term refers to regulation by mRNA or a posttranslational protein modification.

■ Quorum sensing. This term refers to determination of gene expression by bacterial cell density (Fig. 1.5). Quorum sensing is observed in both

— Regulation of Bacterial Virulence: Two-Component Regulator System —

Input signal Bacterial (external milieu) membrane

Regulator protein

— Regulation of Bacterial Virulence: Two-Component Regulator System —

Input signal Bacterial (external milieu) membrane

Regulator protein

Membrane Transmitter Receiver anchor module module

Functional module

Fig. 1.4 A sensor protein integrated in the cytoplasmic membrane receives signals from a receiver module extending into the external milieu, activating the transmitter module. These signals from the external milieu can carry a wide variety of information: pH, temperature, osmolarity, Ca2+, CO2, stationary-phase growth, hunger stress, etc. The transmitter module effects a change in the receiver module of the regulator protein, switching the functional module of the regulator to active status, in which it can then repress or activate the various virulence determinants of a virulence regulon by binding to the different promoter regions. Phosphorylation is commonly used to activate the corresponding sensor and regulator modules.

Virulence regulon

Virulence determinants

Receiver module

Membrane Transmitter Receiver anchor module module

Functional module

Fig. 1.4 A sensor protein integrated in the cytoplasmic membrane receives signals from a receiver module extending into the external milieu, activating the transmitter module. These signals from the external milieu can carry a wide variety of information: pH, temperature, osmolarity, Ca2+, CO2, stationary-phase growth, hunger stress, etc. The transmitter module effects a change in the receiver module of the regulator protein, switching the functional module of the regulator to active status, in which it can then repress or activate the various virulence determinants of a virulence regulon by binding to the different promoter regions. Phosphorylation is commonly used to activate the corresponding sensor and regulator modules.

— Quorum-Sensing Communication in Bacteria (Ceii-to-Ceii Signals)

— Quorum-Sensing Communication in Bacteria (Ceii-to-Ceii Signals)

Acylated Homoserine Lactones

Fig. 1.5 Cell-to-cell signaling is made possible by activation of two genes. The I gene codes for the synthase responsible for synthesis of the autoinducer. The autoinducer (often an N-acyl homoserine lactone) can diffuse freely through the cell membrane. The R gene codes for a transcriptional regulator protein that combines with the autoinducer to become an activator for transcription of various virulence genes.

Fig. 1.5 Cell-to-cell signaling is made possible by activation of two genes. The I gene codes for the synthase responsible for synthesis of the autoinducer. The autoinducer (often an N-acyl homoserine lactone) can diffuse freely through the cell membrane. The R gene codes for a transcriptional regulator protein that combines with the autoinducer to become an activator for transcription of various virulence genes.

Gram-positive and Gram-negative bacteria. It denotes a mode of communication between bacterial cells that enables a bacterial population to react analogously to a multicellular organism.

Accumulation of a given density of a low-molecular-weight pheromone (autoinducer) enables a bacterial population to sense when the critical cell density (quorum) has been reached that will enable it to invade the host successfully, at which point transcription of virulence determinants is initiated.

Was this article helpful?

0 0
Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Post a comment