Molecular basis of host specificity in human pathogenic bacteria

Abstract

Pathogenic bacteria display various levels of host specificity or tropism. While many bacteria can infect a wide range of hosts, certain bacteria have strict host selectivity for humans as obligate human pathogens. Understanding the genetic and molecular basis of host specificity in pathogenic bacteria is important for understanding pathogenic mechanisms, developing better animal models and designing new strategies and therapeutics for the control of microbial diseases. The molecular mechanisms of bacterial host specificity are much less understood than those of viral pathogens, in part due to the complexity of the molecular composition and cellular structure of bacterial cells. However, important progress has been made in identifying and characterizing molecular determinants of bacterial host specificity in the last two decades. It is now clear that the host specificity of bacterial pathogens is determined by multiple molecular interactions between the pathogens and their hosts. Furthermore, certain basic principles regarding the host specificity of bacterial pathogens have emerged from the existing literature. This review focuses on selected human pathogenic bacteria and our current understanding of their host specificity.

Keywords: host specificity; immune evasion; molecular mechanisms; pathogenic bacteria; pathogen–host interactions; tropism.

Figure 1

Cleavage of human IgA1 by bacterial IgA1 proteases. (A) Diagrammatic illustration of human IgA1. Indicated are the hinge region (target for bacterial IgA1 proteases) and the variable and constant regions of the IgA1 light (V_L and C_L) and heavy (V_H and C_H) chains. (B) Amino-acid sequence of the human IgA1 hinge region. The cleavage site for each of the bacterial IgA1 proteases is marked by the species name of the corresponding bacterium.

Figure 2

Schematic illustration of the molecular interactions between microbial pathogens and negative regulator protein factor H of the alternative complement pathway. The 20 FH SCR domains are illustrated in the context of their binding specificities for N. gonorrhoeae,^, N. meningitidis,^, H. influenzae, S. pneumoniae,^,, S. pyogenes,^, S. agalactiae, B. burgdorferi^, and C. albicans. The information on the FH-binding activities was derived from the relevant references cited here for the corresponding microorganisms.

Figure 3

Major requirements for successful infection of human hosts by pathogenic bacteria. (A) Once bacteria enter the host, they need to adhere to mucosal surfaces by recognizing specific receptors on host cells. (B) The bacteria must be able to evade host immune mechanisms for survival (e.g., complement system, antibody) and acquire the necessary nutrients for the growth and expansion of the population (e.g., iron). (C) Once the population size has expanded to a certain level, bacteria can disseminate to other tissues/organs from the initial infection site by intracellular invasion through molecular interactions with host receptors or other means. (D) Some bacteria may be released into the surrounding environments and transmitted to another human host.