Bacterial Virulence Factors: How They Allow Bacteria To Cause More Severe Disease

Introduction

Virulence is a pathogen’s ability to infect a host; alongside this, it causes damage and disease (Sharma et al., 2017). Virulence factors are molecules that enable and assist a pathogen in infecting and damaging their host at a cellular level; bacterial virulence factors typically play a role within the interactions with the host’s cells and tissues or within shielding and protecting the pathogenic bacteria from the host’s defence mechanisms (Wu et al., 2008). Some examples of categories of bacterial virulence factors include toxins, adhesion molecules, resistance factors, and capsules (Wu et al., 2008). Following on from this, these virulence factors can determine the level of severity of the disease this bacteria can cause in their host organisms, they can do this by helping the pathogen evade the host's immune system (Byrne, 2010). Toxins produced by bacteria, are also known as a secretory protein; they can disrupt host immune responses and negatively impacts the host cell’s conditions (Lebrun et al., 2009). Adhesion molecules are membrane proteins, such as pili and fimbriae, these promote bacteria to adhere to host cells easing the process of colonisation (Pizarro-Cerdá and Cossart, 2006). Resistance factors, like the well-known antibiotic resistance, are proteins which have evolved to diminish the effect antimicrobial therapies have on bacteria; this is currently causing a wildlife and public health concern as these infections become more difficult to treat (Sora et al., 2021). Capsules are made from polysaccharides and they surround bacterial cells masking its components to help evade phagocytosis (Wu et al., 2008). Understanding the mechanisms behind how bacterial virulence factors contribute to disease gives us an insight into how they affect severity of the symptoms; this is important for developing effective treatments for our own and the wildlife’s health and welfare. 

Toxins

Bacterial toxins are virulence factors that impact the development and severity of bacterial infections. Toxins can be divided into two categories: endotoxins, which are released from the bacterial cell wall when the bacteria is broken down and lysed, and exotoxins, which are secreted by bacteria during growth being directed to certain proteins and are highly specific to their target (Lebrun et al., 2009). The function of bacterial toxins is to facilitate bacteria in causing damage. Examples of bacterial toxins include epidermolytic toxins, produced by Staphylococcus aureus (S.aureus), these toxins damage the epidermis (e.g. skin) and can cause abscesses (Cheng et al., 2011); and cholera toxin, produced by Vibrio cholerae (V.cholerae), these toxins bind to glycolipids which carry them into the Golgi and Endoplasmic Reticulum, the following processes then disrupt ions and induces intestinal chloride secretion, causing severe diarrhoea (Lencer and Tsai, 2003). Moreover, mechanisms of toxins vary depending on the specific toxin and the host tissue or cell type it targets; some disturb membrane integrity which leads to cell death and tissue damage, and some effect signalling pathways which leads to disruption of immune responses. Some of the targets of these toxins can cause organ dysfunction and system wide impacts (Lacy and Collier, 2002). So, the activities of bacterial toxins on host cells and tissues can lead to more severe disease, as well as damaging symptoms.

Adhesion Molecules

Bacterial adhesion molecules are virulence factors that facilitate the attachment of bacteria to host cells and tissues, helping with the initiation and colonization of the infection. Adhesion molecules can be divided into two categories: pili and fimbriae, which are hair-like organelles that extend from the surface of bacteria. They were initially only found on Gram-negative bacteria, like Escherichia coli (E.coli); they are made of a rod attached to the outer membrane with an adhesion protein at the top determining the binding specificity (Pizarro-Cerdá and Cossart, 2006). Examples of bacterial adhesion molecules include the pili of E.coli, these pili have a protein which binds to a receptor on the epithelial cells of the bladder thus causing bladder inflammation (Sora et al., 2021); and Protein A on S.aureus, which inhibits the attachment of antibodies (Foster and Höök, 1998). Furthermore, adhesion molecules depend on the protein at the tip of the pili or fimbriae; some aid in the formation of bacteria biofilms which increases resistance to the immune response and longevity of the disease (Pizarro-Cerdá and Cossart, 2006, Sora et al., 2021), and some promote colonization which leads to the initiation of the disease and symptoms (Rahme et al., 2000). The adherence of adhesion molecules allow persistence of disease, increasing its severity and longevity.

Resistance Factors

Bacterial resistance factors are virulence factors that have evolved to resist antimicrobial agents and the host’s immune defences (Sora et al., 2021). Two of these factors are: efflux pumps, which pump out antimicrobial agents from the bacterial cell; and enzymes, which degrade or modify antimicrobial agents (Piddock, 2006). Bacterial resistance factors a worrying topic within this field as they allow the bacteria to survive and replicate without being affected by antimicrobial agents, leading to more severe and prolonged infections. Examples of bacterial resistance factors include β-lactamase produced by many gram-negative bacteria like E.coli, which hydrolyse antibiotics such as penicillin and cephalosporins (Sora et al., 2021); and the mecA gene found in bacteria like S.aureus, which has been acquired through horizontal gene transfer and gives resistance to methicillin and other β-lactam antibiotics (Chambers and DeLeo, 2009, Palmer et al., 1991). Moreover, resistance factors are constantly undergoing research where new proteins are being discovered and are being spread by horizontal gene transfer, allowing resistance to more antimicrobial therapies. With increasing resistance to antibiotics and antimicrobial therapies, bacterial resistance factors can allow bacteria to persist for longer in a host; this is extending the time frame of symptoms, inducing a risk for complications, and reducing the chance of an effective treatment (Spellberg and Gilbert, 2014). 

Capsules

Bacterial capsules are virulence factors that are mostly made of a polysaccharide layer surrounding the bacterial cell, these have properties which protect the bacteria against phagocytosis (Wu et al., 2008). There is not as much variation in capsules as we see in other virulence factors; they have the ability to control ion movement into the bacterial cell, protect against lysis, and promote adhesion to cells and inanimate objects (Moxon and Kroll, 1990). The capsule can mask the bacterial cell surface by surrounding and hiding the bacterial antigens, this invokes difficulty for immune cells to recognize and desiccate the bacteria (Merino and Tomás, 2010). Examples of bacterial capsules include the polysaccharide capsule of Streptococcus pneumoniae (S.pneumoniae) which interferes with the hosts mechanisms for engulfment such as phagocytosis (Paton and Trappetti, 2019); and the K antigens of E.coli, which masks the bacterial surface and allows the bacteria to go undetected by the host’s immune response (Jann and Jann, 1987, Kunduru et al., 2016). Hence, the bacteria capsules play important roles involving the interactions between bacteria and its host or its environment (Whitfield, 2006). The envelope around the bacteria creates a safety barrier leading to it being able to withstand immune responses and its environment; then leading to more severe disease. 

Discussion

Bacterial virulence factors including toxins, adhesion molecules, resistance factors, and capsules lead to pathogenic bacteria being able to cause more severe and prolonged disease; this leads to complications such as a weakened immune response to other potential infections. Toxins can cause damage and suppress the host’s immune defences, while adhesion molecules aid in the bacteria’s attachment to the host and initialization of a stable colonization. Resistance factors can allow the bacteria to persist for longer durations therefore reducing the effectiveness of many different types of treatment, while capsules physically protect the bacteria from the hosts immune defences by masking the identifying antigens on the bacteria’s surface. The combination of these virulence factors and the interactions between them all contribute to the establishment and maintenance of severe and long-lasting infections and symptoms. Research and a deep understanding on the mechanisms behind the bacterial virulence factors is important in the journey and development of effective treatments, medications, and prevention of bacterial diseases within the wildlife and our population. Identifying specific virulence factors that are essential for the progress of a bacterial disease can also facilitate the development of targeted therapies. Moreover, the identification and discovery of new virulence factors can provide insights into the infections, mechanisms, and pathways of lesser known bacterial diseases. The recent advances in genomic technologies will be able to further facilitate the identification of new bacterial virulence factors and different interactions between them; this highlights the importance of continued research in this field, to decrease severity and longevity of negatively impactful diseases. 

References