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PubMed1993

Serum protein-binding characteristics of vancomycin.

A synthesis of studies of serum protein binding of vancomycin and its reported abnormal binding in serum with very high concentrations of immunoglobulin A (IgA) suggests that this antibiotic may be bound to more than one serum protein. Using an ultrafiltration method for separating free from bound drug and high-performance liquid chromatography to measure drug concentration, we studied the binding characteristics of vancomycin for alpha-1 acid glycoprotein, IgG, IgM, IgA, and albumin. The results showed that vancomycin does not bind to alpha-1 acid glycoprotein, IgG, or IgM. Major binding to albumin and IgA occurs, and total drug binding to serum proteins can be fully explained by binding to these two proteins. We calculated an N (number of binding sites per molecule) of 1.3 +/- 0.4 and a K (association constant) of 3.3 x 10(5) +/- 6.3 x 10(4) M-1 (NK = 4.3 x 10(5) M-1) for binding to IgA, whereas the corresponding NK value for albumin was only 527.5 M-1, indicating that vancomycin preferentially binds to IgA. Very high concentrations of IgA in serum (i.e., grams per deciliter), such as in patients with IgA myeloma, may result in the paradox of high (total) concentrations of vancomycin in serum that may be clinically ineffective.

Binding Sites↗

PubMed1993

Comparison of ampicillin-sulbactam with vancomycin for treatment of experimental endocarditis due to a beta-lactamase-producing, highly gentamicin-resistant isolate of Enterococcus faecalis.

Increasing antibiotic resistance in the enterococci, including the capacity for beta-lactamase production and the development of high-level aminoglycoside resistance, has complicated the treatment of serious enterococcal infections, which often require synergistic antibiotic combinations for cure. We utilized the rabbit model of aortic valve endocarditis to investigate the effects of various antibiotics, alone and in combination, against a multiply antibiotic-resistant isolate of Enterococcus faecalis. Female New Zealand White rabbits were infected with either a beta-lactamase-producing, gentamicin-resistant isolate of E. faecalis or a non-beta-lactamase-producing, aminoglycoside-susceptible isolate, and the mean log10 CFU per gram of vegetation were determined. The most active agents were low-dose ampicillin-sulbactam (200 mg/kg of body weight per day), high-dose ampicillin-sulbactam (400 mg/kg of body weight per day), and vancomycin (150 mg/kg of body weight per day), which reduced the titers of bacteria by 2.27, 2.76, and 2.85 log10 (CFU/g, respectively, compared with controls. While ampicillin-sulbactam and vancomycin were equally efficacious in reducing titers of bacteria in vegetations, no animals were cured (defined as < 2 log10 CFU/g of vegetation) by either agent, whether treatment was continued for 3 or 7 days. The addition of gentamicin was not associated with increased killing in rabbits infected with the aminoglycoside-resistant isolate. Both high-dose ampicillin-sulbactam and vancomycin regimens demonstrated significant, continued reduction in bacterial titers with the longer periods of treatment (P < or = 0.05); 7-day treatment with high-dose ampicillin-sulbactam produced a greater reduction in bacterial titers in vegetation than 7-day treatment with vancomycin (P < or = 0.05). We conclude that ampicillin-sulbactam and vancomycin are equally effective in the treatment of experimental endocarditis due to beta-lactamase-producing, highly gentamicin-resistant E. faecalis. The optimum therapy for such infections in humans is not known.

Ampicillin↗

PubMed1993

A gene conferring resistance to vancomycin but not teicoplanin in isolates of Enterococcus faecalis and Enterococcus faecium demonstrates homology with vanB, vanA, and vanC genes of enterococci.

We report the sequence of a 630-bp fragment of a gene associated with resistance to high levels of vancomycin in a clinical isolate of Enterococcus faecalis which retained susceptibility to teicoplanin. This gene was similar to the recently sequenced vanB and partially homologous with vanA, but it showed less-marked similarity to vanC. A DNA probe, derived from this polymerase chain reaction-amplified gene fragment, hybridized specifically with genomic DNA from Enterococcus faecium and E. faecalis isolates which were vancomycin resistant (MICs ranged from 8 to 512 micrograms/ml) but susceptible to teicoplanin. Curing of vancomycin resistance was associated with loss of DNA hybridization with the gene probe. Transfer of DNA which hybridized with the probe accompanied transfer of vancomycin resistance to a susceptible recipient strain. Neither curing nor transfer of vancomycin resistance was consistently related to loss or acquisition, respectively, of plasmid DNA.

Amino Acid Sequence↗

PubMed1994

Penetration of vancomycin into mediastinal and cardiac tissues in humans.

Vancomycin penetration into heart tissues (valves, myocardium, auricles, and pericardium) and mediastinal tissues (fat and sternal bone) was evaluated after two regimens of vancomycin administration. Ten patients were given 15 mg of vancomycin per kg of body weight before anesthesia. Ten other patients received the same dose and then a second 7.5-mg/kg dose at the time of initiation of cardiopulmonary bypass. Similar and satisfactory vancomycin tissue penetrations were observed in both groups. However, for some patients in the two groups, vancomycin levels in tissue were less than the MICs for potential pathogens (Staphylococcus aureus and Staphylococcus epidermidis).

Adipose Tissue↗

PubMed1994

Alterations in peptidoglycan precursors and vancomycin susceptibility in Tn917 insertion mutants of Enterococcus faecalis 221.

Derivatives of the highly vancomycin-resistant Enterococcus faecalis strain 221 (MIC, 1,024 micrograms/ml) harboring Tn917 insertions in vanR, vanH, and vanA were compared with the parent strain and the susceptible plasmid-free strain JH2-2 (MIC, 2 micrograms/ml). Cytoplasmic pools of UDP-N-acetyl-muramyl-peptide precursors of strain 221 contained the depsipeptide-terminating precursor as well as elevated levels of both the tripeptide and tetrapeptide precursors. Insertional inactivation of vanR resulted in the loss of carboxypeptidase activity, full susceptibility to vancomycin, and precursor pools similar to those of JH2-2. For the vanA insertional mutant the MBC of vancomycin was fourfold higher than that for JH2-2, and the mutant had increased levels of tripeptide and tetrapeptide precursors compared with those for JH2-2. The vanH insertional mutant showed elevated levels of these precursors, as well as a small amount of depsipeptide, and both the MIC and the MBC of vancomycin were increased compared with those for JH2-2. These findings suggest that DD-carboxypeptidase activity, under the control of vanR, results in increased pools of both tripeptide and tetrapeptide precursors, which may contribute to survival in the presence of vancomycin.

Amino Acid Sequence↗

PubMed1994

Role of tolerance in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis with vancomycin, teicoplanin, and daptomycin.

The role of Staphylococcus aureus tolerance in the treatment and prophylaxis of endocarditis in rats was investigated. The efficacies of vancomycin, teicoplanin, and daptomycin, alone and in combination with rifampin, were compared in rats with endocarditis infected with a tolerant strain of S. aureus and in rats with endocarditis infected with its nontolerant variant. In vitro the cloxacillin-tolerant strain was also tolerant to vancomycin and teicoplanin, but not to daptomycin. However, tolerance to these antibiotics did not influence the results of treatment of experimental S. aureus endocarditis. There was no difference in the bacterial densities in the vegetations of rats infected with either the tolerant or the nontolerant strain after 5 days of treatment with any of the antibiotic regimens. Of all antibiotics, daptomycin was the most effective in reducing bacterial numbers in vegetations. Combination of rifampin with vancomycin or teicoplanin improved the results of treatment for the tolerant as well as the nontolerant strains. Daptomycin was as effective alone as in combination with rifampin. In contrast, tolerance influenced the prophylactic effects of vancomycin and teicoplanin. The proportion of rats with sterile vegetations after prophylaxis with vancomycin or teicoplanin at a low dose was lower for those infected with the tolerant strain than for those infected with the nontolerant strain. A low dose of daptomycin was equally effective against the tolerant and the nontolerant strains. However, higher doses of all three antibiotics afforded almost full protection against both strains.

Animals↗

PubMed1996

Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic.

LY191145 is a p-chlorobenzyl derivative of LY264826 (A82846B) with activity against both vancomycin-susceptible and -resistant enterococci. Incorporation of L-[14C]lysine into peptidoglycan of intact vancomycin-susceptible and -resistant Enterococcus faecium was inhibited by LY191145 (50% inhibitory concentrations of 1 and 5 microgram/ml, respectively). Inhibition was accompanied by accumulation of UDP-muramyl-peptide precursors in the cytoplasm. This agent inhibited late-stage steps in peptidoglycan biosynthesis in permeabilized E. faecium when either the UDP-muramyl-pentapeptide precursor from vancomycin-susceptible E. faecium or the UDP-muramyl-pentadepsipeptide precursor from vancomycin-resistant E. faecium was used as a substrate. Inhibition of late-stage steps led to accumulation of an N-acetyl-[14C]glucosamine-labeled lipid intermediate indicative of inhibition of the transglycosylation step. Inhibition of peptidoglycan polymerization without affecting cross-linking in a particulate membrane-plus-wall-fragment assay from Aerococcus viridans was consistent with this explanation. The fact that inhibition of peptidoglycan biosynthesis by LY191145 was not readily antagonized by an excess of free acyl-D-alanyl-D-alanine or acyl-D-alanyl-D-lactate ligands indicates that the manner in which this compound inhibits transglycosylation may not be identical to that of vancomycin.

Anti-Bacterial Agents↗

PubMed1996

Pharmacodynamics of once- or twice-daily levofloxacin versus vancomycin, with or without rifampin, against Staphylococcus aureus in an in vitro model with infected platelet-fibrin clots.

We compared the pharmacodynamic activities of levofloxacin versus vancomycin, with or without rifampin, in an in vitro model with infected platelet-fibrin clots simulating vegetations. Infected platelet-fibrin clots were prepared with human cryoprecipitate, human platelets, calcium, thrombin, and approximately 10(9) CFU of organisms (MSSA 1199 and MRSA 494) per g and then were suspended via monofilament line into the in vitro model containing Mueller-Hinton growth medium. Antibiotics were administered by bolus injection into the model to simulate human pharmacokinetics; the regimens simulated included levofloxacin at dosages of 800 mg every 24 h (q24h) and 400 mg q12h, vancomycin at 1 g q12h, and rifampin at 600 mg q24h. Each model was run in duplicate over a 72-h period. Infected platelet-fibrin clots were removed in duplicate from each model, weighed, homogenized, serially diluted with sterile 0.9% saline, and plated on tryptic soy agar plates and plates containing antibiotics at 3, 6, and 12 times the MIC to evaluate the emergence of resistance. Time-kill curves were constructed by plotting the inoculum size versus time. Residual inoculum at 72 h was used to compare regimens. All levofloxacin regimens were significantly better than vancomycin monotherapy against both isolates (P < 0.002). Against MSSA 1199, levofloxacin q24h was significantly better than all other regimens, including levofloxacin q12h (P < 0.002); however, no difference between the levofloxacin monotherapy and combination therapy (with rifampin) regimens against MRSA 494 was seen. Killing activity for levofloxacin appeared to correlate better with the peak/MIC ratio than with the area under the curve/MIC ratio. The addition of rifampin significantly enhanced the activity of vancomycin but had little effect upon the activity of levofloxacin. For MRSA 494, vancomycin plus rifampin resulted in the greatest killing (P < 0.05). Development of resistance was not detected with any regimen. Levofloxacin may be a useful therapeutic alternative in the treatment of staphylococcal endocarditis, and further study with animal models of endocarditis or clinical trials are warranted.

Anti-Bacterial Agents↗

PubMed1998

Oral antimicrobial prophylaxis in bone marrow transplant recipients: randomized trial of ciprofloxacin versus ciprofloxacin-vancomycin.

The optimal oral antimicrobial prophylactic regimen for bone marrow transplant recipients remains to be elucidated. We randomized 84 patients to receive either oral ciprofloxacin or ciprofloxacin plus vancomycin at hospital admission. Patients were monitored for bacteremias and clinical parameters, and stool and throat swab surveillance cultures were performed. The addition of vancomycin resulted in a significant decrease in the frequency of patients with surveillance cultures positive for coagulase-negative staphylococci (stool cultures, 44 versus 23%; throat swab cultures, 37 versus 19%) and alpha-hemolytic streptococci (throat swab cultures, 90 versus 60%). The frequencies of positivity for Candida spp. and gram-negative organisms on surveillance cultures were comparable. Despite these results, no differences in the incidences of bacteremias (12 of 41 versus 12 of 43 patients) or clinical parameters such as number of days to first fever, total number of febrile days, length of stay, and number of transfusions could be demonstrated. Because of a lack of efficacy of vancomycin and emerging problems with vancomycin-resistant isolates, vancomycin should not be used in oral antimicrobial prophylaxis regimens.

Antibiotic Prophylaxis↗

PubMed1999

Lysostaphin treatment of experimental aortic valve endocarditis caused by a Staphylococcus aureus isolate with reduced susceptibility to vancomycin.

The rabbit model of endocarditis was used to test the effectiveness of vancomycin and two different lysostaphin dosing regimens for the treatment of infections caused by a Staphylococcus aureus strain with reduced susceptibility to vancomycin (glycopeptide-intermediate susceptible S. aureus [GISA]). Vancomycin was ineffective, with no evidence of sterilization of aortic valve vegetations. However, rates of sterilization of aortic valve vegetations were significantly better for animals treated with either a single dose of lysostaphin (43%) or lysostaphin given twice daily for 3 days (83%) than for animals treated with vancomycin. Rabbits given a single dose of lysostaphin followed by a 3-day drug-free period had mean reductions in aortic valve vegetation bacterial counts of 7.27 and 6.63 log10 CFU/g compared with those for untreated control rabbits and the vancomycin-treated group, respectively. We conclude that lysostaphin is an effective alternative for the treatment of experimental aortic valve endocarditis caused by a clinical VISA strain.

Animals↗

PubMed2002

Comparison of levofloxacin, alatrofloxacin, and vancomycin for prophylaxis and treatment of experimental foreign-body-associated infection by methicillin-resistant Staphylococcus aureus.

The prophylactic and therapeutic activities of two fluoroquinolones, levofloxacin and alatrofloxacin (the L-Ala-L-Ala prodrug of trovafloxacin), were compared to those of vancomycin in two different experimental models of foreign-body-associated infections caused by methicillin-resistant but quinolone-susceptible Staphylococcus aureus (MRSA) isolates. In a guinea pig model of prophylaxis, subcutaneously implanted tissue cages were infected with 10(3) CFU of MRSA, which was a 100% infectious dose in control animals. A single dose of 50 mg of levofloxacin per kg of body weight, administered intraperitoneally 3 h before bacterial challenge, was more efficient than vancomycin for the prevention of infections in tissue cages with MRSA inocula of 10(4) and 10(5) CFU. In a rat model used to evaluate therapy of chronic tissue cage infection caused by MRSA, the efficacies of 7-day high-dose regimens of levofloxacin (100 mg/kg once a day [q.d.] or 50 mg/kg twice a day [b.i.d.]) or alatrofloxacin (50 mg/kg q.d.) were compared to the efficacy of vancomycin (50 mg/kg b.i.d.). Active levels of levofloxacin, trovafloxacin, and vancomycin were continuously present in tissue cage fluid, with the levels exceeding the minimal bactericidal concentrations for MRSA during therapy. The q.d. and b.i.d. regimens of levofloxacin had equivalent activities and were significantly (P < 0.05) more active than alatrofloxacin or vancomycin in decreasing the viable counts of MRSA in tissue cage fluids. No quinolone-resistant mutants emerged during therapy with either fluoroquinolone. The mechanisms explaining the inferior activity of alatrofloxacin compared to the activity of levofloxacin against chronic foreign-body-associated infections by MRSA are unknown.

Animals↗

PubMed2004

Reduced content of lysyl-phosphatidylglycerol in the cytoplasmic membrane affects susceptibility to moenomycin, as well as vancomycin, gentamicin, and antimicrobial peptides, in Staphylococcus aureus.

An association between moenomycin resistance and vancomycin intermediate resistance in Staphylococcus aureus was demonstrated previously. Thus, to elucidate the mechanism of vancomycin intermediate resistance, we searched for factors contributing to moenomycin resistance. Random Tn551 insertional mutagenesis of methicillin-resistant S. aureus strain COL yielded three mutants with decreased susceptibilities to moenomycin. Correspondingly, these mutants also exhibited slightly decreased susceptibilities to vancomycin. Genetic analysis revealed that two of the mutants had Tn551 insertions in the fmtC (mprF) gene, which is associated with the synthesis of lysyl-phosphatidylglycerol. The third Tn551 insertion was located in the lysC gene, which is involved in the biosynthesis of lysine from aspartic acid. Consequently, mutations in both of these loci reduced the lysyl-phosphatidylglycerol content in the cell membrane, giving it a more negative net charge. The positively charged antibiotic gentamicin and cationic antimicrobial peptides such as beta-defensins and CAP18 were more effective against the mutants. The levels of moenomycin and vancomycin binding to intact cells was also greater in the mutants than in the wild type, while the binding affinity was not altered when cells boiled in sodium dodecyl sulfate were used, indicating that both agents had higher affinities for the negatively charged membranes of the mutants. Therefore, the membrane charge of S. aureus appears to influence the efficacies of moenomycin, vancomycin, and other cationic antimicrobial agents.

Anti-Bacterial Agents↗

PubMed2004

Emergence in Asian countries of Staphylococcus aureus with reduced susceptibility to vancomycin.

To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA. hVISA strains were found in India, South Korea, Japan, the Philippines, Singapore, Thailand, and Vietnam. However, neither vancomycin-intermediate S. aureus nor vancomycin-resistant S. aureus isolates were found among MRSA isolates from Asian countries in this survey.

Asia↗

PubMed2004

Population pharmacokinetics of arbekacin, vancomycin, and panipenem in neonates.

Immature renal function in neonates requires antibiotic dosage adjustment. Population pharmacokinetic studies were performed to determine the optimal dosage regimens for three types of antibiotics: an aminoglycoside, arbekacin; a glycopeptide, vancomycin; and a carbapenem, panipenem. Eighty-three neonates received arbekacin (n = 41), vancomycin (n = 19), or panipenem (n = 23). The postconceptional ages (PCAs) were 24.1 to 48.4 weeks, and the body weights (BWs) ranged from 458 to 5,200 g. A one-compartment open model with first-order elimination was applied and evaluated with a nonlinear mixed-effect model for population pharmacokinetic analysis. In the fitting process, the fixed effects significantly related to clearance (CL) were PCA, postnatal age, gestational age, BW, and serum creatinine level; and the fixed effect significantly related to the volume of distribution (V) was BW. The final formulas for the population pharmacokinetic parameters are as follows: CL(arbekacin) = 0.0238 x BW/serum creatinine level for PCAs of <33 weeks and CL(arbekacin) = 0.0367 x BW/serum creatinine level for PCAs of > or = 33 weeks, V(arbekacin) = 0.54 liters/kg, CL(vancomycin) = 0.0250 x BW/serum creatinine level for PCAs of <34 weeks and CL(vancomycin) = 0.0323 x BW/serum creatinine level for PCAs of > or = 34 weeks, V(vancomycin) = 0.66 liters/kg, CL(panipenem) = 0.0832 for PCAs of <33 weeks and CL(panipenem) = 0.179 x BW for PCAs of > or = 33 weeks, and V(panipenem) = 0.53 liters/kg. When the CL of each drug was evaluated by the nonlinear mixed-effect model, we found that the mean CL for subjects with PCAs of <33 to 34 weeks was significantly smaller than those with PCAs of > or = 33 to 34 weeks, and CL showed an exponential increase with PCA. Many antibiotics are excreted by glomerular filtration, and maturation of glomerular filtration is the most important factor for estimation of antibiotic clearance. Clinicians should consider PCA, serum creatinine level, BW, and chemical features when determining the initial antibiotic dosing regimen for neonates.

Aminoglycosides↗

PubMed2005

Evaluation of ceftobiprole in a rabbit model of aortic valve endocarditis due to methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.

Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the methicillin-resistance determinant of staphylococci, and is active against methicillin- and vancomycin-resistant Staphylococcus aureus. Ceftobiprole was compared to vancomycin in a rabbit model of methicillin-resistant S. aureus aortic valve endocarditis. Ceftobiprole and vancomycin were equally effective against endocarditis caused by methicillin-resistant S. aureus strain 76, whereas ceftobiprole was more effective than vancomycin against the vancomycin-intermediate S. aureus strain HIP5836. The activity of ceftobiprole against drug-resistant strains of S. aureus warrants its further clinical development.

Animals↗

PubMed2006

Induction of daptomycin heterogeneous susceptibility in Staphylococcus aureus by exposure to vancomycin.

We studied vancomycin and daptomycin susceptibility in methicillin-resistant Staphylococcus aureus from patients exposed to vancomycin, glycopeptide-intermediate S. aureus, and S. aureus passaged in vancomycin-containing medium. A correlation between vancomycin and daptomycin heteroresistance was noted in some strains, suggesting that exposure of S. aureus to vancomycin may affect susceptibility to daptomycin.

Anti-Bacterial Agents↗

PubMed2004

Mechanism of intrinsic resistance to vancomycin in Clostridium innocuum NCIB 10674.

We have studied the basis for intrinsic resistance to low levels of vancomycin in Clostridium innocuum NCIB 10674 (MIC = 8 microg/ml). Analysis by high-pressure liquid chromatography (HPLC) and mass spectrometry of peptidoglycan nucleotide precursors pools revealed the presence of two types of UDP-MurNac-pentapeptide precursors constitutively produced, an UDP-MurNAc-pentapeptide with a serine at the C terminus which represented 93% of the pool and an UDP-MurNAc-pentapeptide with an alanine at the C terminus which represented the rest of the pool. C. innocuum cell wall muropeptides containing pentapeptide[Ser], either dialanine substituted on the epsilon amino group of lysine or not, were identified and represented about 10% of the monomers while only 1% of pentapeptide[D-Ala] monomers were found. The sequence of a 2,465-bp chromosomal fragment from C. innocuum was determined and revealed the presence of ddl(c. innocuum) and C. innocuum racemase genes putatively encoding homologues of D-Ala:D-X ligases and amino acid racemases, respectively. Analysis of the pool of precursors of Enterococcus faecalis JH2-2, containing cloned ddl(c. innocuum) and C. innocuum racemase genes showed in addition to the UDP-MurNAc-pentapeptide[D-Ala], the presence of an UDP-MurNAc-pentapeptide[D-Ser] precursor. However, the expression of low-level resistance to vancomycin was observed only when both genes were cloned in E. faecalis JH2-2 together with the vanXYc gene from Enterococcus gallinarum BM4174 which encodes a d,d-peptidase which eliminates preferentially the high affinity vancomycin UDP-MurNAc-pentapeptide [D-Ala] precursors produced by the host. We conclude that resistance to vancomycin in C. innocuum NCIB 10674 was related to the presence of the two chromosomal ddl(c. innocuum) and C. innocuum racemase genes allowing the synthesis of a peptidoglycan precursor terminating in serine with low affinity for vancomycin.

Amino Acid Sequence↗

PubMed2004

Revising the role of the pneumococcal vex-vncRS locus in vancomycin tolerance.

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.

ATP-Binding Cassette Transporters↗