Activated Platelets Mediate Monocyte Killing of Klebsiella pneumoniae

Gautam, Iluja; Huss, Chadwick; Storad, Zachary A; Krebs, Michelle; Bassiouni, Omar H; Ramesh, Rochan; Wuescher, Leah M.; Worth, Randall G.

doi:10.1128/iai.00556-22

Cited by 5 publications

(5 citation statements)

References 46 publications

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“…Platelet-eosinophil interactions are involved in EET formation ( 150 , 151 ). Platelet-monocyte aggregate formation is also implicated in sepsis ( 152 ) and the have been shown to mediate killing of Klebsiella pneumonia ( 153 ). In severe COVID-19 ( 154 ) and Dengue ( 155 ) activated platelets activate monocytes and are implicated in disease severity.…”

Section: Beyond Thrombus Formationmentioning

confidence: 99%

“…The role of platelets in infection is a double-edged sword. Platelet activation by bacteria leads to the release of anti-microbial peptides ( 171 ) and also enhances the ability of monocytes to kill Klebsiella pneumoniae ( 153 ) and thus platelets play an important role in preventing sepsis. Thrombus formation acts to trap bacteria and prevent dissemination of the bacteria ( 172 ) although there appears to be an organ-specific effect on the ability to trap Salmonella Typhimurium ( 173 ).…”

Section: Pathogen-induced Platelet Activation: Clinical Implicationsmentioning

confidence: 99%

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Sepsis – it is all about the platelets

Cox

2023

Front. Immunol.

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Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis.

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Section: Beyond Thrombus Formationmentioning

confidence: 99%

Section: Pathogen-induced Platelet Activation: Clinical Implicationsmentioning

confidence: 99%

Sepsis – it is all about the platelets

Cox

2023

Front. Immunol.

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“…Reports of platelets participating in adaptive immunity number more than a few in the literature [ 77 , 78 , 79 , 80 , 81 , 82 ]. Ali et al [ 78 ] provided a comprehensive review of the mammalian platelet and its roles in immunity.…”

Section: Participation In Adaptive Immunitymentioning

confidence: 99%

The Immunological Capacity of Thrombocytes

Ferdous,

Scott

2023

IJMS

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Thrombocytes are numerous in the blood of aves (birds) and ichthyoids (fish). The origin of this cell type is a common hematopoietic stem cell giving rise to a cell that is active in blood coagulation, inflammatory functions, and the immune response in general. It has been well documented that thrombocytes can phagocytize small particles and bacteria. While phagocytosis with an associated oxidative burst has been reported for chicken thrombocytes, some questions remain as to the degradation capacity of phagosomes in ichthyoids. As innate cells, thrombocytes can be stimulated by bacterial, viral, and fungal pathogens to express altered gene expression. Furthermore, there have been observations that led researchers to state that platelets/thrombocytes are capable of serving as “professional antigen presenting cells” expressing CD40, CD80/86, MHC I, and MHC II. This indeed may be the case or, more likely at this time, provide supporting evidence that these cells aid and assist in the role of professional antigen-presenting cells to initiate adaptive immune responses.

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“…However, increased mucoidy blocks binding and internalization by host immune cells, such as macrophages. Therefore, we posit that spontaneous Wzc variants that emerge during infection could represent an invasive sub-population capable of resisting host defenses in the bloodstream or organs ( 52 ). This is supported by evidence that rmpD- negative ST258 isolates from human bloodstream infections have been identified, which exhibit increased mucoidy, encode Wzc variants, and escape phagocytosis ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Urine-mediated suppression of Klebsiella pneumoniae mucoidy is counteracted by spontaneous Wzc variants altering capsule chain length

Khadka,

Ring,

Walker

et al. 2023

mSphere

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Klebsiella pneumoniae is a hospital-associated pathogen primarily causing urinary tract infections (UTIs), pneumonia, and septicemia. Two challenging lineages include the hypervirulent strains, causing invasive community-acquired infections, and the carbapenem-resistant classical strains, most frequently isolated from UTIs. While hypervirulent strains are often characterized by a hypermucoid phenotype, classical strains usually present with low mucoidy. Since clinical UTI isolates tend to exhibit limited mucoidy, we hypothesized that environmental conditions may drive K. pneumoniae adaptation to the urinary tract and select against mucoid isolates. We found that both hypervirulent K. pneumoniae and classical Klebsiella UTI isolates significantly suppressed mucoidy when cultured in urine without reducing capsule abundance. A genetic screen identified secondary mutations in the wzc tyrosine kinase that overcome urine-suppressed mucoidy. Over-expressing Wzc variants in trans was sufficient to boost mucoidy in both hypervirulent and classical Klebsiella UTI isolates. Wzc is a bacterial tyrosine kinase that regulates capsule polymerization and extrusion. Although some Wzc variants reduced Wzc phospho-status, urine did not alter Wzc phospho-status. Urine does, however, increase K. pneumoniae capsule chain length diversity and enhance cell-surface attachment. The identified Wzc variants counteract urine-mediated effects on capsule chain length and cell attachment. Combined, these data indicate that capsule chain length correlates with K. pneumoniae mucoidy and that this extracellular feature can be fine-tuned by spontaneous Wzc mutations, which alter host interactions. Spontaneous Wzc mutation represents a global mechanism that could fine-tune K. pneumoniae niche-specific fitness in both classical and hypervirulent isolates. IMPORTANCE Klebsiella pneumoniae is high-priority pathogen causing both hospital-associated infections, such as urinary tract infections, and community-acquired infections. Clinical isolates from community-acquired infection are often characterized by a tacky, hypermucoid phenotype, while urinary tract isolates are usually not mucoid. Historically, mucoidy was attributed to capsule overproduction; however, recent reports have demonstrated that K. pneumoniae capsule abundance and mucoidy are not always correlated. Here, we report that human urine suppresses K. pneumoniae mucoidy, diversifies capsule polysaccharide chain length, and increases cell surface association. Moreover, specific mutations in the capsule biosynthesis gene, wzc , are sufficient to overcome urine-mediated suppression of mucoidy. These Wzc variants cause constitutive production of more uniform capsular polysaccharide chains and increased release of capsule from the cell surface, even in urine. These data demonstrate that K. pneumoniae regulates capsule chain length and cell surface attachment in response host cues, which can alter bacteria-host interactions.

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Activated Platelets Mediate Monocyte Killing of Klebsiella pneumoniae

Cited by 5 publications

References 46 publications

Sepsis – it is all about the platelets

Sepsis – it is all about the platelets

The Immunological Capacity of Thrombocytes

Urine-mediated suppression of Klebsiella pneumoniae mucoidy is counteracted by spontaneous Wzc variants altering capsule chain length

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