An 18-month-old boy is evaluated for recurrent infections. He has been hospitalized 3 times with pneumonia since age 3 months. He has also had multiple skin infections requiring treatment with antibacterial and antifungal agents. During his last episode of pneumonia, he developed a large pleural effusion, which was drained. The pleural fluid revealed numerous neutrophils containing a large number of intact gram-positive cocci. The microorganisms responsible for this patient's recurrent infections most likely produce which of the following virulence factors?

Question

An 18-month-old boy is evaluated for recurrent infections.  He has been hospitalized 3 times with pneumonia since age 3 months.  He has also had multiple skin infections requiring treatment with antibacterial and antifungal agents.  During his last episode of pneumonia, he developed a large pleural effusion, which was drained.  The pleural fluid revealed numerous neutrophils containing a large number of intact gram-positive cocci.  The microorganisms responsible for this patient's recurrent infections most likely produce which of the following virulence factors?

Quizplus · Accepted Answer

11ec160b_37b9_61c6_9249_a3fd8eccd34c_MD0001_00 This infant with recurrent pulmonary and skin infections likely has a primary immunodeficiency disorder. The presence of a large number of intact bacteria inside the neutrophils suggests chronic granulomatous disease (CGD), an X-linked recessive immunodeficiency marked by impaired NADPH oxidase activity. NADPH oxidase resides on the plasma membrane of neutrophils and is incorporated into the membrane of the phagolysosome during phagocytosis; it catalyzes the formation of superoxide free radicals, which subsequently destroy engulfed pathogens (eg, fungi, bacteria) as part of the oxidative burst. Because patients with CGD have impaired NADPH oxidase activity, they are not able to efficiently destroy bacteria and fungi following phagocytosis; therefore, microscopy will often reveal intact microbes in the neutrophil phagolysosome during active infection. Patients with CGD are most susceptible to catalase-positive organisms, particularly Staphylococcus aureus, Burkholderia, Serratia, Nocardia, and Aspergillus. Catalase degrades hydrogen peroxide into water and oxygen, which reduces oxidative damage and protease activation by reactive oxygen species. Although most pathogenic bacteria and fungi produce catalase, catalase-positive organisms pose a particular risk to patients with CGD because they require higher levels of free radicals (ie, greater NADPH oxidase function) for effective killing. (Choice B) S aureus produces coagulase, which binds to prothrombin and increases conversion of fibrinogen to fibrin. Fibrin subsequently coats the exterior of the organism, which helps it evade phagocytosis. Although patients with CGD are at elevated risk for S aureus, most of the other common pathogens in CGD do not produce coagulase. (Choice C) Lecithinase (alpha toxin) is the major virulence factor of Clostridium perfringens; it causes hydrolysis of membrane phospholipids, activating inflammatory pathways that increase platelet and leukocyte aggregation in the adjacent microvasculature, leading to vasoocclusion and ischemic necrosis. (Choice D) Lipopolysaccharide, a major virulence factor in the outer membrane of gram-negative bacteria, is not present in the gram-positive bacteria (eg, S aureus, Nocardia) and fungal organisms (eg, Aspergillus) that usually infect patients with CGD. (Choice E) The polysaccharide capsule is a major virulence factor for Streptococcus pneumoniae, Neisseria meningitidis, and certain strains of Haemophilus influenzae. Its primary role is to inhibit opsonophagocytosis. The most common pathogens in CGD (eg, S aureus, Nocardia, Aspergillus) do not contain a polysaccharide capsule. Educational objective: Chronic granulomatous disease is a primary immunodeficiency due to impaired NADPH oxidase, an enzyme that generates reactive oxygen species in phagolysosomes. Diminished intracellular killing within neutrophils leads to susceptibility to recurrent infection with catalase-producing bacteria (eg, Staphylococcus aureus, Nocardia) and fungi (eg, Aspergillus). __________ References: Chronic granulomatous disease. (http://www.ncbi.nlm.nih.gov/pubmed/29630223)

An 18-Month-Old Boy Is Evaluated for Recurrent Infections