Complement killing of clinical Klebsiella pneumoniae isolates is serum concentration dependent.
Microbes Infect
; 25(4): 105074, 2023 05.
Article
en En
| MEDLINE
| ID: mdl-36336240
ABSTRACT
Klebsiella pneumoniae is an opportunistic gram-negative pathogen causing serious infections, including sepsis. In plasma, activation of the complement cascades is important for killing bacteria. Thirty clinical Klebsiella spp. blood isolates were analyzed for serum susceptibility in 75% normal human serum (NHS). Twenty-two were serum resistant and eight were serum sensitive, and subsequently tested in 5-75% NHS. Two isolates were killed in 5% and the remaining six in 50%-75% NHS. The two 5% sensitive isolates showed binding of complement (C)4 and C3 in 5% NHS with formation of membrane attack complex (MAC). Inhibition of the classical/lectin mediated pathways (CP/LP) using a C4 specific nanobody, hC4Nb8, led to survival of both isolates in 5% NHS. Using nanobody hC3Nb1, inhibiting the alternative pathway (AP), the isolates were killed in 5% NHS, and amplification of the CP/LP by AP was not necessary for killing. Sole AP killing of these isolates when inhibiting CP/LP with hC4Nb8 was observed in 50% NHS, stressing the concentration dependent functionality of AP. For the less sensitive isolates, killing required activation of CP/LP and AP demonstrated by inhibition with nanobodies. AP inhibition resulted in no C3 deposition on the serum resistant isolate, supporting that AP was the sole activation pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas del Sistema Complemento
/
Klebsiella pneumoniae
Límite:
Humans
Idioma:
En
Revista:
Microbes Infect
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
MICROBIOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Dinamarca