Bacterial Defense against Phagocytosis (2022)

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Bacterial Defense against Phagocytosis (1)

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BacterialDefense against Phagocytosis© Kenneth Todar, PhD

Introduction

Some pathogenic bacteria are inherently able to resist thebactericidalcomponents of host tissues, usually as a function of some structuralproperty.For example, the poly-D-glutamate capsule of Bacillus anthracisprotects the organisms against action of cationic proteins (defensins)in sera or in phagocytes. The outer membrane of Gram-negative bacteriais a permeability barrier to lysozyme and is not easily penetrated byhydrophobiccompounds such as bile salts in the GI tract that are harmful to thebacteria.Pathogenic mycobacteria have a waxy cell wall that resists attack ordigestionby most tissue bactericides. And intact lipopolysaccharides (LPS) ofGram-negativepathogens may protect the cells from complement-mediated lysis or theactionof lysozyme.

Most successful pathogens, however, possess additional structural orbiochemical features that allow them to resist the host cellulardefenseagainst them, i.e., the phagocytic and immune responses. If a pathogenbreaches the host's surface defenses, it must then overcome the host'sphagocytic response to succeed in an infection.

Ability of Pathogens to Avoid or OvercomePhagocytes

Microorganisms invading tissues are first and foremost exposed tophagocytes.Bacteria that readily attract phagocytes and that are easily ingestedand killed are generally unsuccessful as pathogens. In contrast, mostbacteria that are successful as pathogens interfere to some extent withthe activities of phagocytes or in some way avoid their attention.

Bacterial pathogens have devised numerous and diverse strategies toavoid phagocytic engulfment and killing. Most are aimed at blocking oneor more of the steps in phagocytosis, thereby halting the process. Theprocess of phagocytosis is discussed in the chapter on InnateImmunity against bacterial pathogens.

Avoiding Contact with Phagocytes

(Video) Immune Cells Eating Bacteria (Phagocytosis)

Bacteria can avoid the attention of phagocytes in a number of ways.

1. Pathogens may invade or remain confined in regionsinaccessibleto phagocytes. Certain internal tissues (e.g. the lumens of glands,the urinary bladder) and surface tissues (e.g. unbroken skin) are notpatrolledby phagocytes.

2. Some pathogens are able to avoid provoking an overwhelminginflammatoryresponse. Without inflammation the host is unable to focus thephagocyticdefenses.

3. Some bacteria or their products inhibit phagocyte chemotaxis.For example, Streptococcal streptolysin (which also kills phagocytes)suppressesneutrophil chemotaxis, even in very low concentrations. Fractions of Mycobacteriumtuberculosis are known to inhibit leukocyte migration. The Clostridiumø toxin also inhibits neutrophil chemotaxis.

4. Some pathogens can cover the surface of the bacterial cell with acomponent which is seen as "self" by the host phagocytes and immunesystem.Such a strategy hides the antigenic surface of the bacterialcell.Phagocytes cannot recognize bacteria upon contact and the possibilityofopsonization by antibodies to enhance phagocytosis is minimized. Forexample,pathogenic Staphylococcus aureus produces cell-bound coagulaseand clumping factorwhichclots fibrin on the bacterial surface. Treponema pallidum, theagentof syphilis, binds fibronectin to its surface. Group A streptococci areable to synthesize a capsule composed of hyaluronic acid. Hyaluronicacidis the ground substance (tissue cement) in connective tissue. Somepathogens have or can deposit sialic acid residues on their surfaceswhich prevents opsonization by complement components and impedesrecognition by phagocytes.

Inhibition of Phagocytic Engulfment

Some bacteria employ strategies to avoid engulfment (ingestion) ifphagocytesdo make contact with them. Many important pathogenic bacteria bear ontheirsurfaces substances that inhibit phagocytic adsorption or engulfment.Clearlyit is the bacterial surface that matters. Resistance to phagocyticingestionis usually due to a component of the bacterial cell surface (cell wall,or fimbriae, or a capsule). Classical examples of antiphagocyticsubstanceson bacterial surfaces include:

1. Polysaccharide capsules of S. pneumoniae, Haemophilusinfluenzae, Treponema pallidum and Klebsiellapneumoniae

2. M protein and fimbriae of Group A streptococci

3. Surface slime (polysaccharide) produced as a biofilm byPseudomonasaeruginosa

4. O polysaccharide associated with LPS of E. coli

(Video) Bacteria resisting phagocytic destruction

5. K antigen (acidic polysaccharides) of E. coli ortheanalogous Vi antigen of Salmonella typhi

6. Cell-bound or soluble Protein A produced by Staphylococcusaureus. Protein A attaches to the Fc region of IgG and blocks thecytophilic(cell-binding) domain of the Ab. Thus, the ability of IgG to act as anopsonic factor is inhibited, and opsonin-mediated ingestion of thebacteriais blocked.

Survival Inside of Cells

Some bacteria survive inside of phagocytes, either neutrophils ormacrophages. Bacteria that can resist killing and survive ormultiplyinside of phagocytes or other cells are considered intracellularparasites. The intracellular environment of a phagocyte may be aprotective one, protectingthebacteria during the early stages of infection or until they develop afullcomplement of virulence factors. The intracellular environment alsoguardsthebacteria against the activities of extracellular bactericides,antibodies,drugs, etc. Some bacteria that are intracellular parasites because theyable to invade eucaryotic cells are listedinTable 1.

Table 1. BACTERIAL INTRACELLULARPATHOGENS

Organism Disease
Mycobacteriumtuberculosis Tuberculosis
Mycobacteriumleprae Leprosy
Listeriamonocytogenes Listeriosis
Salmonellatyphi Typhoid Fever
Shigelladysenteriae Bacillary dysentery
Yersinia pestis Plague
Brucella species
Brucellosis
Legionellapneumophila Pneumonia
Rickettsiae Typhus; Rocky Mountain Spotted Fever
Chlamydia Chlamydia; Trachoma

Some intracellular parasites have special genetically-encodedmechanismsto get themselves into host cells that are nonphagocytic. Pathogenssuch as Yersinia, Listeria, E. coli, Salmonella,Shigellaand Legionella possess complex machinery for cellular invasionandintracellular survival. These systems involve various types ofnon-toxinvirulence factors. Sometimes these factors are referred to as bacterialinvasins.Still other bacteria such as Bordetella pertussis and Streptococcuspyogenes, have recently been discovered in the intracellularhabitatof epithelial cells.

Legionella pneumophila enters mononuclear phagocytes bydepositingcomplement C3b on its surfaces and using that host protein to serveas a ligand for binding to macrophage cell surfaces. After ingestion,the bacteriaremain in vacuoles that do not fuse with lysosomes, apparently due totheinfluence of soluble substances produced by the bacteria.

Salmonella bacteria possesses an invasin operon (invA - H)thatencodes for factors that regulate their entry into host cells.Mutationsin the operon yield organisms that can adhere to target cells withoutbeinginternalized. This suggests that one or more of the invproteinsstimulates signal transduction in the host cell that results engulfmentof the salmonellae. A similar invasin gene in Yersinia is knownto encode a protein that both promotes adherence and activates thecytochalasin-dependentengulfment process. This invasin can confer invasive capacity onnoninvasiveE.coli, and even latex particles.

Intracellular parasites survive inside of phagocytes by virtue ofmechanismswhich interfere with the bactericidal activities of the host cell. Someof these bacterial mechanisms include:

1. Inhibition of fusion of the phagocytic lysosomes (granules)withthe phagosome. The bacteria survive inside of phagosomes becausetheyprevent the discharge of lysosomal contents into the phagosomeenvironment.Specifically, phagolysosome formation is inhibited in the phagocyte.Thisis the strategy employed by Salmonella, M. tuberculosis,Legionellaand the chlamydiae.

-With M. tuberculosis, bacterial cell wall components(sulfatides)are thought to be released from the phagosome that modify lysosomalmembranesto inhibit fusion.

-In Chlamydia, some element of the bacterial (elementarybody)wall appears to modify the membrane of the phagosome in which it iscontained.

(Video) How Pathogens Evade the Immune System

-In L. pneumophila, as with the chlamydia, some structuralfeatureof the bacterial cell surface, already present at the time of entry(ingestion),appears to modify the membranes of the phagosomes, thus preventingtheirmerger with lysosomal granules. In Legionella, it is known thata single gene is responsible for the inhibition of phagosome lysosomefusion.

-In Salmonella typhimurium, the pH that develops in thephagosomeafter engulfment actually induces bacterial gene products that areessentialfor their survival in macrophages.

2. Survival inside the phagolysosome. With someintracellularparasites, phagosome-lysosome fusion occurs, but the bacteria areresistantto inhibition and killing by the lysosomal constituents. Also, someextracellularpathogens can resist killing in phagocytes utilizing similar resistancemechanisms. Little is known of how bacteria can resist phagocytickillingwithin the phagocytic vacuole, but it may be due to the surfacecomponentsof the bacteria or due to extracellular substances that they producewhichinterfere with the mechanisms of phagocytic killing. Some examples ofhowcertain bacteria (both intracellular and extracellular pathogens)resistphagocytic killing are given below.

-Mycobacteria (including M. tuberculosis and Mycobacteriumleprae) grow inside phagocytic vacuoles evenafterextensive fusion with lysosomes. Mycobacteria have a waxy,hydrophobiccell wall containing mycolic acids and other lipids, and are not easilyattacked by lysosomal enzymes.

-Cell wall components (LPS?) of Brucella abortus apparentlyinterferewith the intracellular bactericidal mechanisms of phagocytes.

-B. abortus and Staphylococcus aureus are vigorouscatalaseand superoxide dismutase producers, which might neutralize the toxicoxygenradicals that are generated by the NADPH oxidase and MPO systems inphagocytes.S.aureus also produces cell-bound pigments (carotenoids) that"quench"singlet oxygen produced in the phagocytic vacuole.

-The outer membrane and capsular components of Gram-negativebacteria(e.g. Salmonella, Yersinia, Brucella, E.coli)can protect the peptidoglycan layer from the lytic activity oflysozyme.

-Some pathogens (e.g. Salmonella, E. coli) are knowntoproduce extracellular iron-binding compounds (siderophores)whichcan extract Fe+++ from lactoferrin (or transferrin) andsupply iron tocells for growth.

-Bacillus anthracis resists killing and digestion by means ofits capsule which is made up of poly-D-glutamate. The "unnatural"configurationof this polypeptide affords resistance to attack bycationicproteins or conventional proteases and prevents the deposition ofcomplement on the bacterial surface.

Escape from the phagosome. Early escape from the phagosomevacuoleis essential for growth and virulence of some intracellular pathogens.

-This is a clever strategy employed by the Rickettsiae. Rickettsiaenter host cells in membrane-bound vacuoles (phagosomes) but are freeinthe cytoplasm a short time later, perhaps in as little as 30 seconds. Abacterial enzyme, phospholipase A, may be responsible for dissolutionofthe phagosome membrane.

(Video) Role of phagocytes in innate or nonspecific immunity | NCLEX-RN | Khan Academy

-Listeria monocytogenes relies on several molecules for earlylysis of the phagosome to ensure their release into the cytoplasm.Theseinclude a pore-forming hemolysin (listeriolysin O) and two forms ofphospholipaseC. Once in the cytoplasm, Listeria induces its own movementthrougha remarkable process of host cell actin polymerization and formation ofmicrofilaments within a comet-like tail.

-Shigella also lyses the phagosomal vacuole and inducescytoskeletalactin polymerization for the purpose of intracellular movement andcell to cellspread.

Products of Bacteria that Kill or DamagePhagocytes

One obvious strategy in defense against phagocytosis is directattackby the bacteria upon the professional phagocytes. Any of the substancesthat pathogens produce that cause damage to phagocytes have beenreferredto as aggressins. Most of these are actually extracellularenzymesor toxins that kill phagocytes. Phagocytes may be killed by a pathogenbefore or after ingestion.

Killing Phagocytes Before Ingestion

Many Gram-positive pathogens, particularly the pyogenic cocci,secreteextracellular substances that kill phagocytes, acting either as enzymesor "pore-formers" that lyse phagocyte membrane. Some of thesesubstances are described ashemolysinsor leukocidins because of their lethal action against red blood cellsor leukocytes.

-Pathogenic streptococci produce streptolysin. StreptolysinObinds to cholesterol in membranes. The effect on neutrophils is tocauselysosomal granules to explode, releasing their lethal contents into thecellcytoplasm.

-Pathogenic staphylococci produce leukocidin, which alsoactson the neutrophil membrane and causes discharge of lysosomal granules.

-Extracellular proteins that inhibit phagocytosis include the ExotoxinA of Pseudomonas aeruginosa which kills macrophages, andthebacterial exotoxins that are adenylate cyclases (e.g. anthrax toxin EFand pertussis toxin AC) which decrease phagocytic activity throughdisruption of cell equilibrium and consumption of ATP reserves neededfor engulfment.

Killing Phagocytes After Ingestion. Some bacteria exert theirtoxic action on the phagocyte after ingestion has taken place. They maygrow in the phagosome and release substances which can pass through thephagosome membrane and cause discharge of lysosomal granules, or theymaygrow in the phagolysosome and release toxic substances which passthroughthe phagolysosome membrane to other target sites in the cell. Manybacteriathat are the intracellular parasites of macrophages (e.g. Mycobacterium,Brucella,Listeria)usually destroy macrophages in the end, but the mechanisms are notcompletelyunderstood.

Other Antiphagocytic Strategies Used byBacteria

The foregoing has been a discussion of the most commonly-employedstrategiesof bacterial defense against phagocytes. Although there are few clearexamples,some other antiphagocytic strategies or mechanisms probably exist. Forexample, a pathogen may have a mechanism to inhibit the production ofphagocytesor their release from the bone marrow.

(Video) AS level. J.1 Defence against disease and phagocytosis Ms Cooper

A summary of bacterial mechanisms for interference with phagocytesisgiven in the table below.

Table 2. BACTERIALINTERFERENCEWITHPHAGOCYTES
BACTERIUM TYPE OF INTERFERENCE MECHANISM
Streptococcus pyogenes Kill phagocyte Streptolysin induces lysosomal discharge intocell cytoplasm

Inhibit neutrophil chemotaxis Streptolysin is chemotactic repellent

Resist engulfment (unless Ab is present) M Protein on fimbriae

Avoid detection by phagocytes Hyaluronic acid capsule
Staphylococcus aureus Kill phagocyte Leukocidin lyses phagocytes and induceslysosomal dischargeinto cytoplasm

Inhibit opsonized phagocytosis Protein A blocks Fc portion of Ab;polysaccharide capsule insome strains

Resist killing Carotenoids, catalase, superoxide dismutasedetoxify toxicoxygen radicals produced in phagocytes

Inhibit engulfment Cell-bound coagulase hides ligands forphagocytic contact
Bacillus anthracis Kill phagocytes or undermine phagocyticactivity
Anthrax toxin EF

Resist engulfment and killing Capsular poly-D-glutamate
Streptococcus pneumoniae Resist engulfment (unless Ab is present) Capsular polysaccharide
Klebsiella pneumoniae Resist engulfment Polysaccharide capsule
Haemophilus influenzae Resist engulfment Polysaccharide capsule
Pseudomonas aeruginosa Kill phagocyte Exotoxin A kills macrophages; Cell-boundleukocidin

Resist engulfment Alginate slime and biofilm polymers
Salmonella typhi Resist engulfment and killing Vi (K) antigen (microcapsule)
Salmonella enterica (typhimurium)
Survival inside phagocytes Bacteria develop resistance to low pH,reactive forms ofoxygen, andhost "defensins" (cationic proteins)
Listeria monocytogenes Escape from phagosome Listeriolysin, phospholipase C lyse phagosomemembrane
Clostridium perfringens Inhibit phagocyte chemotaxis ø toxin

Inhibit engulfment Capsule
Yersinia pestis Resist engulfment and/or killing Protein capsule on cell surface
Yersinia enterocolitica Kill phagocytes Yop proteins injected directly intoneutrophils
Mycobacteria Resist killing and digestion Cell wall components prevent permeation ofcells; solublesubstances detoxify of toxic oxygen radicals and preventacidificationof phagolysosome
Mycobacterium tuberculosis Inhibit lysosomal fusion Mycobacterial sulfatides modify lysosomes
Legionella pneumophila Inhibit phagosome-lysosomal fusion Unknown
Neisseria gonorrhoeae Inhibit phagolysosome formation; possiblyreduce respiratoryburst Involves outer membrane protein (porin) P.I
Rickettsia Escape from phagosome Phospholipase A
Chlamydia Inhibit lysosomal fusion Bacterial substance modifies phagosome
Brucella abortus Resist killing Cell wall substance (LPS?)
Treponema pallidum Resist engulfment Polysaccharide capsule material
Escherichia coli Resist engulfment O antigen (smooth strains); K antigen (acidpolysaccharide)

Resist engulfment and possibly killing K antigen
Textbook of Bacteriology Index

FAQs

Bacterial Defense against Phagocytosis? ›

Some bacteria resist phagocytic destruction by preventing fusion of the lysosome with the phagosome

phagosome
A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes.
https://en.wikipedia.org › wiki › Phagosome
. Some bacteria resist phagocytic destruction by escaping from the phagosome before the lysosome fuses. Some bacteria resist phagocytic destruction by preventing acidification of the phagosome.

How do bacteria protect themselves from phagocytosis? ›

The bacteria secrete the extracellular fibrinogen binding protein (Efb), which binds the serum protein fibrinogen (137). In this way, the bacterium creates a proteinaceous shield that covers the surface bound opsonin and prevents phagocytosis (137, 138) (Figure ​ 4).

What is protective against phagocytosis? ›

One obvious strategy in defense against phagocytosis is direct attack by the bacteria upon the professional phagocytes. Any of the substances that pathogens produce that cause damage to phagocytes have been referred to as aggressins. Most of these are actually extracellular enzymes or toxins that kill phagocytes.

How does bacterial capsule prevent phagocytosis? ›

Capsules can protect a bacterial cell from ingestion and destruction by white blood cells (phagocytosis). While the exact mechanism for escaping phagocytosis is unclear, it may occur because capsules make bacterial surface components more slippery, helping the bacterium to escape engulfment by phagocytic cells.

What fights infection through phagocytosis? ›

Macrophages work as innate immune cells through phagocytosis and sterilization of foreign substances such as bacteria, and play a central role in defending the host from infection.

How can bacteria protect itself? ›

Bacteria can defend themselves against infection by bacteriophages using an adaptive immune system called CRISPR-Cas. This immune system was only discovered in the last decade, and is present in about half of the bacterial species that we know so far.

How do bacteria evade host defenses? ›

Bacteria are multifaceted in their methods used to escape immune detection. They employ tactics such as modulating their cell surfaces, releasing proteins to inhibit or degrade host immune factors, or even mimicking host molecules.

Which virulence factors enables bacteria to avoid phagocytosis by white blood cells? ›

Bacterial Infectivity

Factors that are produced by a microorganism and evoke disease are called virulence factors. Examples are toxins, surface coats that inhibit phagocytosis, and surface receptors that bind to host cells.

What host defense is prevented by the capsule of some pathogenic bacteria? ›

Due to its exposure to the environment capsules are thought to have roles in the virulence and colonisation of a number of pathogenic bacteria. Capsules can help to prevent bacterial desiccation, foil phagocytosis by host cells or reduce complement-mediated lysis.

What characteristic allows the virus to often successfully resist phagocytosis? ›

What characteristic allows the virus to often successfully resist phagocytosis but induce a strong antibody response that usually results in neutralization of the pathogen? Viruses are often too small to be recognized by phagocytes.

Which cells do not perform phagocytosis? ›

So, the correct answer is 'Basophil'.

What are the 4 steps of phagocytosis? ›

Phagocytosis can be divided into four main steps: (i) recognition of the target particle, (ii) signaling to activate the internalization machinery, (iii) phagosome formation, and (iv) phagolysosome maturation.

Which of the following structures help bacteria escape phagocytosis? ›

THE GLYCOCALYX ENABLES CERTAIN BACTERIA TO RESIST PHAGOCYTIC ENGULFMENT BY WHITE BLOOD CELLS IN THE BODY OR IN SOIL AND WATER. THE GLYCOCALYX ALSO ENABLES SOME BACTERIA TO ADHERE TO ENVIRONMENTAL SURFACES (ROCKS, ROOT HAIRS, TEETH, ETC.), COLONIZE, AND RESIST FLUSHING.

How do some bacteria survive by escaping the killing action of macrophages? ›

Once in the phagosome of the macrophage the bacterium uses its type 3 secretion system to inject proteins that prevent the lysosomes from fusing with the phagosomes, thus providing a safe haven for Salmonella replication within the phagosome and protecting the bacteria from antibodies and other defense elements.

Do bacteria use phagocytosis? ›

The particles commonly phagocytosed by white blood cells include bacteria, dead tissue cells, protozoa, various dust particles, pigments, and other minute foreign bodies.

Which virulence factors enables bacteria to avoid phagocytosis by white blood cells? ›

Bacterial Infectivity

Factors that are produced by a microorganism and evoke disease are called virulence factors. Examples are toxins, surface coats that inhibit phagocytosis, and surface receptors that bind to host cells.

Videos

1. Cell Defence: Lymphocytes and Phagocytes
(Science Sauce)
2. Neutrophils - the professional phagocytes and first defense of our body
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3. Phagocytosis
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4. Amazing video : Bacterial Phagocytosis by Macrophages and Neutrophils
(Biology)
5. How do Immune Cells (Macrophages) Engulf Bacteria Phagocytosis Process
(Code Scientia)
6. Immune response against Bacteria
(Animated biology With arpan)

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