RELATIONSHIPS AMONG CAPSULAR STRUCTURE, PHAGOCYTOSIS, AND MOUSE VIRULENCE IN KLEBSIELLA-PNEUMONIAE

被引:89
作者
KABHA, K
NISSIMOV, L
ATHAMNA, A
KEISARI, Y
PAROLIS, H
PAROLIS, LAS
GRUE, RM
SCHLEPPERSCHAFER, J
EZEKOWITZ, ARB
OHMAN, DE
OFEK, I
机构
[1] TEL AVIV UNIV,SACKLER FAC MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL
[2] RHODES UNIV,SCH PHARMACEUT SCI,GRAHAMSTOWN 6140,SOUTH AFRICA
[3] UNIV KONSTANZ,FAC BIOL,D-78434 CONSTANCE,GERMANY
[4] HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT MED & PEDIAT,BOSTON,MA 02115
[5] UNIV TENNESSEE,DEPT MICROBIOL & IMMUNOL,MEMPHIS,TN 38163
[6] VET ADM MED CTR,MEMPHIS,TN 38163
关键词
D O I
10.1128/IAI.63.3.847-852.1995
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Klebsiella pneumoniae strains of the K2 capsular serotype are usually highly virulent in mice, which is in contrast to the low virulence of most other serotypes. Here we used a genetic approach to examine the relative contribution of capsule type to the virulence of K. pneumoniae in mice. We used wild-type strains expressing capsular polysaccharide ICPS) serotypes K2 (strain KPA1) and E21a (strains KPB1 and KPC1), which were then used to construct capsule-switched derivatives. The close proximity of the cps gene cluster to selectable his markers made it possible to mobilize the cps genes by conjugation from one serotype (donor) to another (recipient) and to obtain recombinants in which interserotype switching had occurred by reciprocal recombination. Each capsule-switched derivative examined of the RPA and KPC strain backgrounds produced a CPS that was immunologically and structurally identical to that of the donor. Strain background was confirmed by demonstrating restriction fragment length polymorphism patterns identical to those of the respective recipients. The parent strains were then compared with capsule-switched recombinants for phenotypic properties associated with virulence. Clearance from the bloodstreams of mice was rapid in serotype K21a strains of either wild-type or recombinant origin, whereas K2 strains remained viable in the blood during the period examined. These differences appeared to be dependent upon the CPS type but independent of strain background. Binding to macrophages was higher in K21a strains than in those with the K2 capsule and was also independent of the strain background. Both blood clearance and macrophage-binding activities were completely inhibited by yeast mannan, suggesting that they were mediated via the macrophage mannose receptor. The K2 parent strain was highly virulent to mice (50% lethal dose [LD(50)], 3 x 10(3)), while the K21a parent strains demonstrated low virulence (LD(50), >2 x 10(8)). Interestingly, the virulence of recombinant KPC10(cpsK2), originally of the KPCl(cpsK21a) background, was intermediate (LD(50), 4 x 10(5)). In contrast, both cpsK21a recombinants of the originally virulent KPA1(cpsK2) background became nearly avirulent (LD(50), >2 x 10(8)). Six additional serotypes (K12, K24, K32, K55, K62, and K67) were examined, and all showed a positive correlation between the ability of the Klebsiella serotype to interact with a human mannose receptor, as expressed by Cos I cell recombinants, and the LD(50) of the serotype. These results suggest that expression of a capsule which is recognized by the mannose receptor markedly affects the interaction with macrophages and blood clearance. The virulence of the cpsK2 recombinant of the KPC background may have been enhanced because it was expressing a heterologous capsule not recognized by the mannose receptor. Thus, this study shows that the capsule type plays an important role in the rate of blood clearance and phagocytosis but contributes only partially to the virulence of K. pneumoniae in mice.
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收藏
页码:847 / 852
页数:6
相关论文
共 27 条
[1]   MOLECULAR-CLONING OF A CD28 CDNA BY A HIGH-EFFICIENCY COS CELL EXPRESSION SYSTEM [J].
ARUFFO, A ;
SEED, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8573-8577
[2]   CARBOHYDRATE-SPECIFIC RECEPTORS OF THE LIVER [J].
ASHWELL, G ;
HARFORD, J .
ANNUAL REVIEW OF BIOCHEMISTRY, 1982, 51 :531-554
[3]   LECTINOPHAGOCYTOSIS OF ENCAPSULATED KLEBSIELLA-PNEUMONIAE MEDIATED BY SURFACE LECTINS OF GUINEA-PIG ALVEOLAR MACROPHAGES AND HUMAN MONOCYTE-DERIVED MACROPHAGES [J].
ATHAMNA, A ;
OFEK, I ;
KEISARI, Y ;
MARKOWITZ, S ;
DUTTON, GGS ;
SHARON, N .
INFECTION AND IMMUNITY, 1991, 59 (05) :1673-1682
[4]  
BENACERRAF B, 1959, J EXP MED, V110, P24
[5]   SEROEPIDEMIOLOGY OF KLEBSIELLA BACTEREMIC ISOLATES AND IMPLICATIONS FOR VACCINE DEVELOPMENT [J].
CRYZ, SJ ;
MORTIMER, PM ;
MANSFIELD, V ;
GERMANIER, R .
JOURNAL OF CLINICAL MICROBIOLOGY, 1986, 23 (04) :687-690
[6]  
DUTTON GGS, 1989, CARBOHYD RES, P147
[7]   MOLECULAR CHARACTERIZATION OF THE HUMAN MACROPHAGE MANNOSE RECEPTOR - DEMONSTRATION OF MULTIPLE CARBOHYDRATE RECOGNITION-LIKE DOMAINS AND PHAGOCYTOSIS OF YEASTS IN COS-1 CELLS [J].
EZEKOWITZ, RAB ;
SASTRY, K ;
BAILLY, P ;
WARNER, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (06) :1785-1794
[8]   CLONING AND EXPRESSION IN PSEUDOMONAS-AERUGINOSA OF A GENE INVOLVED IN THE PRODUCTION OF ALGINATE [J].
GOLDBERG, JB ;
OHMAN, DE .
JOURNAL OF BACTERIOLOGY, 1984, 158 (03) :1115-1121
[9]   EFFECT OF GENETIC SWITCHING OF CAPSULAR TYPE ON VIRULENCE OF STREPTOCOCCUS-PNEUMONIAE [J].
KELLY, T ;
DILLARD, JP ;
YOTHER, J .
INFECTION AND IMMUNITY, 1994, 62 (05) :1813-1819