The battle with the host over microbial size

https://doi.org/10.1016/j.mib.2013.01.001 Get rights and content

An eponymous feature of microbes is their small size, and size affects their pathogenesis. The recognition of microbes by host factors, for example, is often dependent on the density and number of molecular interactions occurring over a limited surface area. As a consequence, certain antimicrobial substances, such as complement, appear to target particles with a larger surface area more effectively. Although microbes may inhibit these antimicrobial activities by minimizing their effective size, the host uses defenses such as agglutination by immunoglobulin to counteract this microbial evasion strategy. Some successful pathogens in turn are able to prevent immune mediated clearance by expressing virulence factors that block agglutination. Thus, microbial size is one of the battlegrounds between microbial survival and host defense.

Highlights

► Microbial size varies and is a factor in interaction with a host. ► Small microbial size allows for evasion of important host defenses. ► Several host defenses function by increasing effective microbial size. ► Some pathogens are able to evade defenses that target their small size.

Introduction

Members of the microbial world span a great range of shapes and sizes. The selective value of microbial shape has been reviewed elsewhere [1]. Differences in size are used to distinguish species and impact many aspects of microbial physiology and lifestyle. Bacterial cells, for example, range from 0.15 to 700 μm in length. In addition, for single-celled organisms, modulation of cell division or separation may significantly impact their effective size. For microbes residing in a mammalian host, size may be a determining factor in an infectious agent's success or its clearance [2, 3, 4, 5]. Many successful pathogens have evolved strategies to modulate their effective size to accommodate these challenges [6]. The host in turn appears to target the ability of microbes to escape its defenses with their small size. By analyzing bacteria differing only in effective size it is possible to sort out some of the independent contributions of size to pathogenesis. These studies reveal that microbial size is a battleground in the interaction between pathogen and host.

Section snippets

Why microbial size matters

Most microbes are generally small to minimize their cellular volume and grow most efficiently. While prokaryotic species with large or giant cell morphology may be found in nature, these forms are generally not observed within mammalian hosts. However, pathogens that are typically small may form larger individual cells under certain growth conditions (Table 1). When cell division or septation is inhibited, long filamentous forms that may be 10–50 times longer than usual may result. Filamentous

The host fights back

Although microbes may take advantage of their small surface area to evade key defenses such as the complement system, other aspects of the host response appear to circumvent this strategy. For example, the bivalent or multivalent binding of immunoglobulin agglutinates microbial targets to increase their effective size (Table 1). This process is demonstrated by the ‘threading reaction’, which refers to the inhibition of separation of daughter cells by the bridging of bound immunoglobulin during

Evasion of host defenses based on size

If the immune response subverts the small effective size of microbes, are there ways that successful pathogens evade these defense mechanisms? The agglutinating effect of immunoglobulin requires antigen recognition, while diversity and variation of microbial surfaces provide a means of avoiding binding by antibody. Not all classes of immunoglobulin are equivalent in their ability to agglutinate a target. On the mucosal surface, the most abundant antibody class is IgA, which is quadravalent in

Conclusions

In summary, size may have a pronounced impact the interaction of microbes with their host. Successful pathogens may alter their effective size to evade clearance or promote adhesive interactions (Figure 1). The host, in turn, may subvert the plasticity of microbes and their ability use their size as an advantage. Pathogenesis studies that rely on viable counts of organism in culture and do not routinely incorporate the use of microscopy are unlikely to control for the effects of microbial size

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgement

This work was supported by the U.S. Public health Service grant numbers AI38446 and AI78538 to JNW.

References (31)

  • S. Justice et al.

    Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis

    Proc Natl Acad Sci USA

    (2004)
  • L. Okagaki et al.

    Cryptococcal cell morphology affects host cell interactions and pathogenicity

    PLoS Pathog

    (2010)
  • O. Zaragoza et al.

    Fungal cell gigantism during mammalian infection

    PLoS Pathog

    (2010)
  • S. Justice et al.

    Morphological plasticity as a bacterial survival strategy

    Nat Rev Microbiol

    (2008)
  • T. Bjarnsholt et al.

    Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

    Microbiology

    (2005)
  • Cited by (25)

    • The impact of bacterial size on their survival in the presence of cationic particles of nano-silver

      2020, Journal of Trace Elements in Medicine and Biology
      Citation Excerpt :

      Microbial pathogens have evolved a variety of strategies to evade host defenses. One such strategy used by invading microbes is the expanding of cell size to combat host defenses [1,2]. Among microbes, bacterial pathogens can effectively expand their surface area through different mechanisms, including expanding the cellular diameter, elongating into filaments or producing prosthecae to avoid phagocytosis and enhanced interaction to host cell surfaces [3–5].

    • Intestinal Bile Acids Induce a Morphotype Switch in Vancomycin-Resistant Enterococcus that Facilitates Intestinal Colonization

      2019, Cell Host and Microbe
      Citation Excerpt :

      In S. pneumoniae, a mechanism of morphotype switching was proposed that balances distinct advantages of short and long chains. Longer chains have the disadvantage of an increased probability of being bound by complement and of coming into contact with phagocytic host cells; however, the increased surface area of longer chains may also advantageously increase adherence to host surfaces (Weiser, 2013). In a zebrafish model of systemic infection, long-chain autolysin mutants of E. faecalis were less virulent and more susceptible to phagocytosis (Salamaga et al., 2017).

    • Staphylococcus aureus Aggregation and Coagulation Mechanisms, and Their Function in Host–Pathogen Interactions

      2016, Advances in Applied Microbiology
      Citation Excerpt :

      As S. aureus possess several mechanisms that prevent complement deposition and activation on its surface (reviewed in Zipfel & Skerka, 2014), it is likely that this pathogen is not affected by the potentially increased complement deposition on larger clumps. Second, agglutination of bacteria by host antibodies is essential for efficient pathogen clearance in many diseases (Weiser, 2013; Yang, Blair, & Salama, 2016), and when S. aureus is agglutinated by specific antibodies or pulmonary surfactant proteins, it has been shown to increase phagocytosis (Hartshorn et al., 1998; Varrone et al., 2014). However, these host-induced agglutinates are relatively small [up to couple dozen cells (Varrone et al., 2014)] and differ in composition from the clumps induced by fibrinogen binding.

    • Quantification of filamentation by uropathogenic Escherichia coli during experimental bladder cell infection by using semi-automated image analysis

      2015, Journal of Microbiological Methods
      Citation Excerpt :

      The biological significance of the filamentous phenotype of human pathogens is in many instances unclear. Several studies however indicate that filamentation, as for the marine organisms, is an intended morphology which provides a survival advantage to the bacterium (reviewed in Justice et al., 2008; Weiser, 2013; Young, 2006). Filamentation by human pathogens has been suggested to occur due to activation of the SOS-response (D'Ari, 1985) triggered by DNA damage during infection (Eriksson et al., 2003; Justice et al., 2006).

    View all citing articles on Scopus
    View full text