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1.
Vancomycin is used increasingly to treat invasive infections caused by multidrug-resistant Streptococcus pneumoniae. Although no vancomycin-resistant strains have been isolated to date, tolerant strains that fail to die rapidly and that cause relapsing disease have been described. The vex123-pep27-vncRS locus, consisting of an ABC transporter, a presumed signaling peptide, and a two-component system, respectively, has been implicated in vancomycin tolerance. Recent findings, however, challenged this model. The data presented here indicate that erythromycin in the growth medium induces a vancomycin-tolerant phenotype and that loss of function of Pep27 or VncRS does not alter autolysis. However, a role for the ABC transporter encoded by the vex123 genes in tolerance was confirmed. A vex3 mutant was considerably more tolerant to vancomycin treatment than the wild-type strain T4, and the strength of the phenotype depended on the orientation of the resistance cassette used to construct the mutant. Microarray results suggested a number of genes that might be involved in tolerance in the vex3 mutant. Although the exact function and regulation of the vex123-pep27-vncRS locus remains to be determined, several factors influence the autolysis behavior of S. pneumoniae, including the bacterial capsule, erythromycin, and the lytA and vex3 gene products.  相似文献   

2.
Several mutants of Streptococcus pneumoniae were isolated that appeared tolerant, to varying extents, to the lytic and bactericidal effects of some antibiotics that inhibit peptidoglycan synthesis, but were not deficient in autolytic activity. The method used to select the mutants was based on the survival of tolerant mutants during treatment with either bacitracin, benzylpenicillin, D-cycloserine plus beta-chloro-D-alanine, or vancomycin. Most (60 to 80%) of the surviving isolates were found to be deficient in autolytic activity, and these were rejected. The smaller proportion that had wild-type sensitivity to deoxycholate-induced lysis was studied further with respect to tolerance to the other antibiotics used in the selection procedures. Two of these mutants (selected by treatment with benzylpenicillin) were tolerant to either benzylpenicillin or D-cycloserine plus beta-chloro-D-alanine, but were supersusceptible, in terms of initiation of lysis, to either bacitracin or vancomycin. The minimal inhibitory concentration values of several antibiotics for these two mutants were identical to those for the wild-type strain. Moreover, the interaction of radioactive benzylpenicillin with the penicillin-binding proteins, examined in whole organisms, also appeared the same as previously found for either wild-type or autolytic-deficient strains of S. pneumoniae.  相似文献   

3.
Vancomycin therapy failure due to the emergence of tolerance in pneumococci is increasing. The molecular mechanism of tolerance is not clear, but lytA and pep27 are known to be involved. Our aim was to evaluate the expression of both genes in vancomycin-tolerant Streptococcus pneumoniae (VTSP) strains. Eleven VTSP strains from a total of 309 clinical isolates of S. pneumoniae from 1997 to 2006 were classified according to the criteria of Liu and Tomasz. All VTSP strains were evaluated for susceptibility according to CLSI criteria, serotype by the Quellung test, and clonality by PFGE. The expressions of lytA and pep27 were analyzed in different growth phases by RT-PCR with and without vancomycin. Eighty-two percent of VTSP strains showed resistance to penicillin, and 100% were sensitive to vancomycin and cefotaxime. The most frequent serotypes of VTSP strains were 23F (4/11) and 6B (3/11). Clonal relationship was observed in only two strains. No significant changes were observed in pep27 expression in the three phases of growth in VTSP strains with and without vancomycin. Interestingly, pep27 expression in the stationary phase in the non-tolerant reference strain R6 was significantly higher. However, no significant differences in lytA expression were observed between VTSP and R6 strains during the phases of growth analyzed. The absence of changes in pep27 expression in VTSP strains in the stationary phase may be related to their ability to tolerate high antibiotic concentrations, and thus, they survive and remain in the host under the antibiotic selective pressure reflected in therapeutic failure.  相似文献   

4.
The extent to which autolytic microbial enzymes are involved in the fate of microorganisms ingested by phagocytes has not been determined. It is known, however, that activation of degradative enzymes occurs during certain microbicidal events. We examined the possible role of the pneumococcal autolytic enzyme (an N-acetylmuramyl-L-alanine amidase) in the loss of viability and degradation of pneumococci during phagocytosis by rabbit polymorphonuclear leukocytes. Three bacterial systems were compared: (a) wild type pneumococci with an active autolytic system; (b) wild type bacteria grown under conditions that block the endogenous autolytic activity and (c) a mutant strain defective in the major autolytic enzyme of this bacterium. No differences could be detected between the autolysis-positive and negative bacteria in the rate of killing and in the fate of macromolecular cell constituents during ingestion by rabbit peritoneal polymorphonuclear leukocytes.  相似文献   

5.
Vancomycin is frequently added to standard therapy for pneumococcal meningitis. Although vancomycin‐resistant Streptococcus pneumoniae strains have not been isolated, reports on the emergence of vancomycin‐tolerant pneumococci are a cause of concern. To date, the molecular basis of vancomycin tolerance in S. pneumoniae is essentially unknown. We examined two vancomycin‐tolerant clinical isolates, i.e. a purported autolysin negative (LytA), serotype 23F isolate (strain S3) and the serotype 14 strain ‘Tupelo’, which is considered a paradigm of vancomycin tolerance. S3 was characterized here as carrying a frameshift mutation in the lytA gene encoding the main pneumococcal autolysin. The vancomycin tolerance of strain S3 was abolished by transformation to the autolysin‐proficient phenotype. The original Tupelo strain was discovered to be a mixture: a strain showing a vancomycin‐tolerant phenotype (Tupelo_VT) and a vancomycin‐nontolerant strain (Tupelo_VNT). The two strains differed only in terms of a single mutation in the ciaH gene present in the VT strain. Most interestingly, although the vancomycin tolerance of Tupelo_VT could be overcome by increasing the LytA dosage upon transformation by a multicopy plasmid or by externally adding the autolysin, we show that vancomycin tolerance in S. pneumoniae requires the simultaneous presence of a mutated CiaH histidine kinase and capsular polysaccharide.  相似文献   

6.
The binding of bactericidal antibiotics like penicillins, cephalosporins, and glycopeptides to their bacterial targets stops bacterial growth but does not directly cause cell death. A second process arising from the bacteria itself is necessary to trigger endogenous suicidal enzymes that dissolve the cell wall during autolysis. The signal and the trigger pathway for this event are completely unknown. Using S. pneumoniae as a model, we demonstrate that signal transduction via the two-component system VncR/S triggers multiple death pathways. We show that the signal sensed by VncR/S is a secreted peptide, Pep27, that initiates the cell death program. These data depict a novel model for the control of bacterial cell death.  相似文献   

7.
A comparative hybridization protocol was used to isolate a small segment of DNA present in the Streptococcus pneumoniae type 19F strain SSZ but absent from strain Rx1, a nonencapsulated derivative of the type 2 strain D39. This segment of DNA is a 1,747-bp insertion sequence, designated IS1202, flanked by 23-bp imperfect inverted repeats and containing a single open reading frame sufficient to encode a 54.4-kDa polypeptide. A 27-bp target sequence is duplicated at either end of the element. IS1202 is not related to any of the currently known insertion elements and is the first reported for S. pneumoniae. Although found predominantly in type 19F strains in up to five copies, it has also been shown to be present in the chromosomes of pneumococci belonging to other serotypes. One of the four IS1202 copies in the encapsulated strain SSZ is located 1,009 bp downstream of the dexB gene, and transformation studies reveal that it is also closely linked to the type 19F capsular polysaccharide synthesis (cps) locus.  相似文献   

8.
A spontaneous mutant of Bacillus subtilis 168, SR3, tolerant to the autolysis-inducing action of sucrose monoesters of long-chain fatty acids, was isolated. It was shown that its susceptibility to the lytic action of sucrose esters and glycerol esters of short-chain fatty acids, fatty acids themselves, some surfactants, uncouplers of oxidative phosphorylation, and β-lactam antibiotics against the mutant strain was similar to that of the wild-type strain. In the absence of sucrose monoesters, no substantial differences were observed between the mutant and the wild-type strains in cell autolysis and autolysin activity. It was found that in the mutant the cellular uptake of the molecules of sucrose ester of palmitic acid was suppressed. Also, a protein having a molecular weight of 41 kDa was richer in the membrane of strain SR3 than that of 168. The tolerance of the mutant to the lytic action of the ester is suggested to be derived from a decrease in the amount of ester molecules transferred into the membrane, where the activity of autolytic enzymes may be controlled.  相似文献   

9.
The two pneumococcal autolytic enzymes (an N-acetylmuramoyl-L-alanine amidase and an endo-beta-1,4-N-acetylglucosaminidase) are directly involved in the penicillin-induced killing of Streptococcus pneumoniae. The activity of these lytic enzymes was efficiently controlled in tolerant mutants under physiological conditions.  相似文献   

10.
AIMS: To evaluate the autolytic phenotype of Bacillus thuringiensis. METHODS AND RESULTS: The autolytic rate of 87 strains belonging to different subsp. of B. thuringiensis was examined at pH 6, 6.5 and 8.5 in different buffers under starvation conditions. At pH 6 the extent of autolysis (average in the strain collection 38.3 +/- 21.1) was strain-dependent with wide variability, while at pH 6.5 and 8.5 (averages 72.0 +/- 9.0 and 63.1 +/- 8.2, respectively) it was much more uniform with only a few strains showing low autolytic rates. Forty-one per cent of the strains showed high resistance (>/=80%) to mutanolysin, a commercial muramidase from Streptomyces. The peptidoglycan hydrolase pattern was evaluated by renaturing SDS-PAGE using cells of B. thuringiensis subsp. tolworthi HD125 as indicator. The strain collection showed seven major lytic bands of about 90, 63, 46, 38, 32, 28 and 25 kDa, and in the stationary growth phase (72 h) there was a more intense 25 kDa band in the autolytic pattern. Using Micrococcus lysodeicticus and Listeria monocytogenes as the indicators lytic activity was retained, as seen by the bands of 63, 46, 38, 32 and 25 kDa. Growth in the different media did not affect the autolytic pattern. NaCl abolished the activity of all the peptidoglycan hydrolases in the gel, but in the presence of KCl, MgCl(2), MnCl(2) and EDTA some activity was retained. At basic pH the lytic activity increased. CONCLUSIONS: The autolytic phenotype of B. thuringiensis was found to be strain-dependent, and different proteins exibited peptidoglycan hydrolase activity, particularly at alkaline pH. Several of these proteins retained lytic activity against other bacterial species. SIGNIFICANCE AND IMPACT OF THE STUDY: The characterisation of the autolytic phenotype of B. thuringiensis should expand the prospects of using this species in bacterial bio-control and field applications.  相似文献   

11.
The glycopeptide antibiotic teicoplanin belongs to the same group as vancomycin and ristocetin and is a valuable tool for studying the autolytic system of sensitive Gram-positive bacteria. Teicoplanin, at a concentration of 1 microgram ml-1, caused rapid lysis of exponential phase cells of Streptococcus faecalis. Bacillus spp. were most sensitive to the antibiotic; effective lysis occurred at 0.1 microgram teicoplanin ml-1. The bacteriolytic effect depended on the antibiotic concentration, the growth phase and growth rate of the target organism. Antibiotic added to overnight cultures did not cause lysis. Mg2+ (50 mM) was unable to prevent lysis. Mutants with decreased autolytic activity were more resistant to teicoplanin and lysed more slowly than the wild-type. Growth of bacteria in slightly acidic medium protected the cells against the lytic effect of teicoplanin typically observed at pH 7 or 8. This pH-dependent antibiotic tolerance was demonstrated with both bacilli and streptococci. Bacterial lysis was prevented by the presence of Ac-L-Lys(Ac)-D-Ala-D-Ala and normal growth was observed when this peptide was added simultaneously with teicoplanin. Bacteria pretreated with teicoplanin, washed and transferred to fresh medium or buffers behaved as if the antibiotic was still present; in neutral or slightly alkaline conditions strong lysis occurred, whereas in acidic buffer only bacteriostasis was observed. In contrast to vancomycin, teicoplanin induced some lysis of bacteria in hypertonic media, presumably by affecting the integrity of the cell membrane.  相似文献   

12.
The autolytic enzyme (an N-acetylmuramyl-L-alanine amidase) of a clinical isolate, strain 101/87, which is classified as an atypical pneumococcus, has been studied for the first time. The lytA101 gene coding for this amidase (LYTA101) has been cloned, sequenced, and expressed in Escherichia coli. The LYTA101 amidase has been purified and shown to be similar to the main autolytic enzyme (LYTA) present in the wild-type strain of Streptococcus pneumoniae, although it exhibits a lower specific activity, a higher sensitivity to inhibition by free choline, and a modified thermosensitivity with respect to LYTA. Most important, in contrast with the LYTA amidase, the activity of the LYTA101 amidase was inhibited by sodium deoxycholate. This property is most probably responsible of the deoxycholate-insensitive phenotype shown by strain 101/87. Phenotypic curing of strain 101/87 by externally adding purified LYTA or LYTA101 amidase restored in this strain some typical characteristics of the wild-type strain of pneumococcus (e.g., formation of diplo cells and sensitization to lysis by sodium deoxycholate), although the amount of the LYTA101 amidase required to restore these properties was much higher than in the case of the LYTA amidase. Our results indicate that modifications in the primary structure or in the mechanisms that control the activity of cell wall lytic enzymes seem to be responsible for the characteristics exhibited by some strains of S. pneumoniae that have been classically misclassified and should be now considered atypical pneumococcal strains.  相似文献   

13.
Sortase A (SrtA) is required to anchor neuraminidase, beta-galactosidase, and possibly other LPXTG motif proteins to the pneumococcal cell surface. We examined the role of SrtA in Streptococcus pneumoniae nasopharyngeal (NP) colonization in the chinchilla model. The srtA mutant colonized the nasopharynx at a significantly lower level than the D39 parent strain during the second and third week of the carriage, and was eliminated from nasopharynx one week earlier than the D39 pneumococci. Our data indicate that SrtA contributes to pneumococcal NP colonization in this animal model.  相似文献   

14.
The mechanism of synergy between vancomycin and penicillin, as well as other beta-lactam antibiotics, was examined in a penicillin-resistant E. faecium (D366) expressing an inducible low-level resistance to vancomycin. It was demonstrated that penicillin per se was not able to reduce the inducible expression of the 39.5-kDa protein (VANB) or the carboxypeptidase activity which are involved in the mechanism of vancomycin resistance of this strain. Assays of competition between 3H-benzylpenicillin and diverse beta-lactam antibiotics suggested as the most likely explanation of the synergy that, once vancomycin resistance has been induced, the high-molecular mass penicillin-binding proteins (PBPs), and possibly PBP1 in particular, which have a high affinity for beta-lactam antibiotics, take over the role of the low-affinity PBP5 which is, in the non-induced strain, responsible for beta-lactam resistance.  相似文献   

15.
M J Kennedy  P A Volz 《Sabouraudia》1985,23(4):265-273
Mice were treated orally with various antibiotics to determine which members of the indigenous intestinal microflora normally suppress Candida albicans colonization and dissemination from the gastrointestinal (GI) tract. The mice were given penicillin, clindamycin, vancomycin, erythromycin, or gentamicin for 3 days, and then challenged orally with C. albicans. Penicillin, clindamycin, and vancomycin, but not gentamicin or erythromycin, decreased the total anaerobic bacterial populations in the animals ceca, and increased the enteric bacilli population levels. All three of the former antibiotics allowed C. albicans to proliferate in the gut and, subsequently, disseminate from the GI tract to visceral organs. The ability of C. albicans to associate with intestinal mucosal surfaces was also tested. It was found that antibiotics which reduced anaerobic population levels, but not enteric bacilli or aerobes, also predisposed animals to mucosal association by C. albicans. It is suggested that the strictly anaerobic bacterial populations which predominate in the gut ecosystem are responsible for the inhibition of C. albicans adhesion, colonization and dissemination from the GI tract.  相似文献   

16.
Certain erythromycin-resistant strains of Staphylococcus aureus remain sensitive to other macrolide antibiotics. If these strains are exposed to low levels of erythromycin, resistance to other antibiotics is induced. The antibiotics to which resistance is induced by erythromycin include: other macrolides as well as lincosaminide, streptogramin (group B) antibiotics but not chloramphenicol, amicetin, streptogramin (group A) antibiotics, tetracyclines, and aminoglycosides. Hence erythromycin induces resistance exclusively towards inhibitors of 50S ribosomal subunit function and, thus far, only with respect to three of six known classes of inhibitors which act on this subunit. In the four strains tested, erythromycin did not induce resistance to pactamycin or bottromycin, to fusidic acid (which inhibits a function involving both subunits), or to other antibiotics which do not inhibit ribosomal function. Thus, by inducing resistance erythromycin could antagonize the action of other antibiotics, and a consistent pattern of antagonism was observed to each antibiotic class in all of the strains in which this could be tested, as well as to other antibiotic members of the same chemical class in each bacterial strain.  相似文献   

17.
A wild-type strain of Micrococcus radiodurans and its nonpigmented mutant W(1) were tested for sensitivity to 10 antibiotics selected from the standpoint of their mechanism of action. Representatives of groups of antibiotics inhibiting deoxyribonucleic acid (DNA) synthesis, DNA-dependent ribonucleic acid synthesis, protein synthesis, and cell wall synthesis were selected. M. radiodurans and its mutant exhibited full susceptibility to all antibiotics tested (mitomycin C, actinomycin D, chloramphenicol, dihydrostreptomycin, erythromycin, neomycin, kanamycin, benzylpenicillin, bacitracin, and vancomycin), the degree of susceptibility being of the same order as that of a standard strain of Staphylococcus aureus 209 P, with the exception of dihydrostreptomycin.  相似文献   

18.
目的研究侵袭性和非侵袭性肺炎链球菌的耐药谱的差异,指导合理应用抗生素及感染管理。方法回顾性统计分析2009至2011年来天台县人民医院就诊患者分离肺炎链球菌的标本来源及耐药性,比较侵袭性和非侵袭性肺炎链球菌耐药率之间的差异。结果共分离出肺炎链球菌642株,痰液中分离出584株,非痰液中分离出58株,其中血液中分离出32株,脑脊液中分离出20株,其他分离出6株,所有肺炎链球菌对万古霉素和利奈唑胺均敏感,对青霉素、红霉素、克林霉素、四环素及复方新诺明耐药严重,对左氧氟沙星、氯霉素比较敏感;侵袭性分离株对青霉素、红霉素、克林霉素、左氧氟沙星、四环素及氯霉素的耐药率显著高于非侵袭性肺炎链球菌。结论该院分离的肺炎链球菌主要来自痰液标本,耐青霉素肺炎链球菌的检出率高,大环内酯类耐药严重,存在一定比例的侵袭性感染,非侵袭菌株与侵袭性菌株耐药谱之间存在一定差异,临床治疗应该区别对待,系统的监测细菌耐药性,合理选择抗菌药物。  相似文献   

19.
Although pneumococcal conjugate vaccines are close to being licensed, a more profound knowledge of the virulence factors responsible for the morbidity and mortality caused by Streptococcus pneumoniae is necessary. This review deals with the major structures of pneumococci involved in the pathogenesis of pneumococcal disease and their interference with the defense mechanisms of the host. It is well known that protection against S. pneumoniae is the result of phagocytosis of invading pathogens. For this process, complement and anticapsular polysaccharide antibodies are required. Besides, relatively recent experimental data suggest that protection is also mediated by the removal of disintegrating pneumococci and their degradation products (cell wall, pneumolysin). These structures seem to be major contributors to illness and death caused by pneumococci. An effective conjugate vaccine should therefore preferably include the capsular polysaccharide and at least one of these inflammatory factors.  相似文献   

20.
Abstract Bacitracin and other antibiotics that inhibit late stages in peptidoglycan biosynthesis induce vancomycin resistance in a high-level, inducibly vancomycin-resistant strain of Enterococcus faecium . Exposure to bacitracin led to synthesis of the lactate-containing UDP-MurNAc-pentadepsipeptide precursor required for vancomycin resistance. These findings indicate that inhibition of peptidoglycan biosynthesis can lead to induction of vancomycin resistance and raise the possibility that multiple signals may serve to induce resistance.  相似文献   

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