What makes staph and strep resist phagocytosis

Many important pathogenic bacteria bear on their surfaces substances that inhibit phagocytic adsorption or engulfment. Clearly it is the bacterial surface that matters.

Resistance to phagocytic ingestion is usually due to a component of the bacterial cell surface cell wall, or fimbriae, or a capsule. Classical examples of antiphagocytic substances on bacterial surfaces include:. Polysaccharide capsules of S. Surface slime polysaccharide produced as a biofilm by Pseudomonas aeruginosa. K antigen acidic polysaccharides of E.

Cell-bound or soluble Protein A produced by Staphylococcus aureus. Thus, the ability of IgG to act as an opsonic factor is inhibited, and opsonin-mediated ingestion of the bacteria is blocked. Table 1. Some intracellular parasites have special genetically-encoded mechanisms to get themselves into host cells that are nonphagocytic. Pathogens such as Yersinia , Listeria , E. These systems involve various types of non-toxin virulence factors.

Sometimes these factors are referred to as bacterial invasins. Still other bacteria such as Bordetella pertussis and Streptococcus pyogenes, have recently been discovered in the intracellular habitat of epithelial cells.

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

Salmonella bacteria possesses an invasin operon inv A - H that encodes for factors that regulate their entry into host cells. Mutations in the operon yield organisms that can adhere to target cells without being internalized. This suggests that one or more of the inv proteins stimulates signal transduction in the host cell that results engulfment of the salmonellae.

A similar invasin gene in Yersinia is known to encode a protein that both promotes adherence and activates the cytochalasin-dependent engulfment process. This invasin can confer invasive capacity on noninvasive E. Intracellular parasites survive inside of phagocytes by virtue of mechanisms which interfere with the bactericidal activities of the host cell.

Some of these bacterial mechanisms include:. Inhibition of fusion of the phagocytic lysosomes granules with the phagosome. The bacteria survive inside of phagosomes because they prevent the discharge of lysosomal contents into the phagosome environment.

Specifically, phagolysosome formation is inhibited in the phagocyte. This is the strategy employed by Salmonella , M. In Legionella , it is known that a single gene is responsible for the inhibition of phagosome lysosome fusion.

Survival inside the phagolysosome. With some intracellular parasites, phagosome-lysosome fusion occurs, but the bacteria are resistant to inhibition and killing by the lysosomal constituents. Also, some extracellular pathogens can resist killing in phagocytes utilizing similar resistance mechanisms.

Little is known of how bacteria can resist phagocytic killing within the phagocytic vacuole, but it may be due to the surface components of the bacteria or due to extracellular substances that they produce which interfere with the mechanisms of phagocytic killing.

Some examples of how certain bacteria both intracellular and extracellular pathogens resist phagocytic killing are given below. Mycobacteria have a waxy, hydrophobic cell wall containing mycolic acids and other lipids, and are not easily attacked by lysosomal enzymes. Salmonella , Yersinia , Brucella , E. The actual number of colony-forming units injected was verified for each experiment by performing colony counts on blood agar plates.

At selected times after infection, mice were killed by CO 2 asphyxiation, and bacteria were enumerated in specific organs by plating fold serial dilutions of tissue homogenates on blood agar plates.

Viable bacterial counts also were determined in the blood of infected mice by collecting blood samples from the tail vein at different times after inoculation and plating serial dilutions in blood agar. To monitor extracellular bacterial growth, samples containing bacteria, but not PMNs, were included in each experiment. PMNs then were lysed by the addition of 1 mL of deionized H 2 O dH 2 O , and viable bacterial counts were determined by plating diluted samples onto blood agar plates.

For the determination of bacterial intracellular survival, PMNs were incubated for 2 h with S. Gentamicin kills extracellularly located S. Subsequently, the samples were extensively washed with PBS, and cells were lysed by the addition of 1 mL of dH 2 O, serially diluted in PBS, and plated to determine the number of viable intracellular bacteria.

Samples containing only bacteria were used to estimate the efficacy of antibiotic killing. Gentamicin protection assay for in vivo detection of viable intracellular S. To determine the viability of S. For this purpose, mice were infected with S. Cell-free bacteria were separated from cell-associated bacteria by differential centrifugation at g for 10 min.

After 1 h, cells were washed 3 times with PBS to eliminate traces of gentamicin, and aliquots either were taken to assess intracellular bacterial viability log 10 colony-forming units of S. Use of cells containing viable S. Mice were either monitored for survival or killed at different times after inoculation, and the bacterial burden was determined in blood and peripheral organs by counting the colony-forming units of S.

Systemic dissemination of S. The mortality of mice was associated with the ability of these strains to disseminate from a local skin lesion to the bloodstream and to establish infection in systemic organs figure 1B. A Survival curves of mice infected with different strains of Streptococcus pyogenes.

Each experimental group consisted of 10 mice. Resistance of S. Therefore, it could be anticipated that the capacity of these strains of S. To assess this possibility, the ability of S. PMNs were isolated from mouse peritoneal exudates and were incubated with S. Determination of bacterial killing by PMNs was performed after 3 h incubation by lysing PMNs with dH 2 O and by plating diluted samples onto blood agar plates.

No significant bacterial killing was observed in samples that contained PMNs, compared with that in control samples that contained medium alone figure 2 , upper panels, black bars. Carrageenan-induced PMNs were incubated in vitro with either S. Colony-forming units of S. Bottom panels Viability of S. Spleens were isolated from mice infected with S. Cell-free bacteria present in the spleen suspensions were separated from cell-associated bacteria by centrifugation.

Both pellet and supernatant were treated with gentamicin for 1 h and extensively washed, and colony-forming units were assessed by plating serial dilutions. For the determination of bacterial intracellular survival, PMNs were infected in vitro with S. Gentamicin added to the culture supernatant does not generally access the intracellular milieu; therefore, intracellular located bacteria are protected from the antibiotic activity [ 18 , 19 ].

PMNs then were washed and lysed with dH 2 O, and viable bacterial counts were determined by plating diluted samples onto blood agar plates. As shown in the upper panels of figure 2 white bars a considerable proportion of microorganisms was associated with PMNs and was intracellularly situated, given that they remained viable after gentamicin treatment. Bacteria incubated in the absence of PMNs were almost completely eradicated after antibiotic treatment, corroborating the susceptibility of these microorganisms to gentamicin.

To assess whether viable S. Spleens were isolated from infected mice at 48 h after infection and turned out into a single-cell suspension, and cell-free bacteria were separated from cell-associated bacteria by centrifugation.

Both pellet cell-associated bacteria and supernatant cell-free bacteria were treated with gentamicin for 1 h, extensively washed, and the colony-forming units were assessed by plating serial dilutions. After treatment, all cell-free bacteria were killed, whereas the intracellular microorganisms were not significantly affected, which indicates that they remain viable inside the phagocytic cells figure 2 , bottom panels.

Spleen cells isolated from mice infected with S. The results see figure 3 show that gentamicin-treated infected spleen cells were able to establish infection in recipient mice to a similar extent as an intravenous infection with a similar number of broth-grown bacteria.

Mice injected either with gentamicin-treated infected spleen cells or with broth-grown bacteria died from infection between days 3 and 5 after inoculation. Mice injected with an equivalent number of uninfected spleen cells were used as controls. Extent of bacteremia figure 3B and bacterial loads in rethiculoendothelial organs figure 3C also were comparable between both groups.

The results see figure 3 represent experiments carried out with S. Capacity of gentamicin-treated spleen cells isolated from mice infected with Streptococcus pyogenes to transfer infection into naive mice. A Survival curves of mice inoculated with either spleen cells isolated from infected mice INFEC cells; black squares , a comparable no.

B Bacteremia in mice intravenously inoculated with either broth-grown bacteria white squares or with cells from infected mice black squares. C Bacterial counts in the tissues of mice infected either with broth-grown bacteria white bars or with cells from infected mice black bars. Purified PMNs isolated from mice infected with S. For this purpose, PMNs were purified from the spleen of mice infected with S.

The results see figure 4A show that all mice inoculated with PMNs purified from spleen of infected mice died between 2 and 3 days after inoculation. The pili fimbriae of Streptococcus pyogenes both blocks the activation of the complement pathways on the bacterial cell wall and helps to resist phagocytic engulfment. The vaccine for Haemophilus influenzae type b contains capsular material from this bacterium.

The body recognizes this capsular material as foreign and produces antibodies against it. Describe how this might this protect the person from infection with this bacterium compared to a person who is not immunized. Human defensins are short cationic peptides amino acids long that are directly toxic by forming pores in the cytoplasmic membrane of a variety of microorganisms causing leakage of cellular needs.

They also activate cells for an inflammatory response. Defensins are produced by leukocytes, epithelial cells, and other cells. They are also found in blood plasma and mucus. Cathelicidinsare proteins produced by skin and mucosal epithelial cells. The two peptides produced upon cleavage of the cathelicidin are directly toxic to a variety of microorganisms.

One pepitide also can bind to and neutralize LPS from Gram-negative cell walls to reduce inflammation. Learning Objectives Briefly describe at least 3 ways capsules may enable bacteria to resist phagocytic engulfment and state how this can promote colonization. State at least 2 mechanisms other than capsules that certain bacteria might use to resist phagocytic engulfment. State 3 ways bacteria might resist antibacterial peptides like defensins.

Highlighted Bacterium Read the description of Haemophilus influenzae and match the bacterium with the description of the organism and the infection it causes. Glycoprotein molecules known as endocytic pattern-recognition receptors are found on the surface of phagocytes. They are so named because they recognize and bind to pathogen-associated molecular patterns - components of common molecules such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, and glucans - found in many microorganisms.

Capsules can cover up these surface molecules preventing their attachment to the endocytic pattern-recognition sites on the phagocyte. Capsules that Interfere with Complement Pathways The capsules of some bacteria interfere with the host's complement pathways and do so in a number of ways: The capsules of some bacteria prevent the formation of C3 convertase, an early enzyme in the complement pathways.

In some bacteria, the capsule covers the opsonin C3b bound to the bacterial cell wall so that it can't bind to C3b receptors called CR1 on the surface of phagocytes. Biofilms Many pathogenic bacteria, as well as normal flora, form complex bacterial communities as biofilms.

By living as a community of bacteria as a biofilm, these bacteria are better able to: resist attack by antibiotics; trap nutrients for bacterial growth and remain in a favorable niche; adhere to environmental surfaces and resist flushing; live in close association and communicate with other bacteria in the biofilm; and resist phagocytosis and attack by the body's complement pathways. Other Mechanisms The M-protein of Streptococcus pyogenes allows these bacteria to be more resistant to phagocytic engulfment.

Many bacteria involved in infection have the ability to co-opt the functions of the host cell to the benefit of the bacterium. This is done by way of bacterial secretions systems that enable the bacterium to directly inject bacterial effector molecules into the cytoplasm of the host cell in order to alter its cellular machinery or cellular communication.