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Streptococcus pneumoniae produced an erysipelas-like eruption in a patient with the nephrotic syndrome. The eruption and accompanying fever resolved upon treatment with aqueous penicillin.
The chloramphenicol resistance of Streptococcus haemolyticus, Streptococcus pneumoniae and Streptococcus faecalis isolated from clinical materials was proved to be due to an inactivating enzyme produced by these bacteria. The inactivated products of chloramphenicol were identified as 1-acetoxy, 3-acetoxy and 1,3-diacetoxy derivatives by thin-layer chromatography and infrared spectroscopy. The responsible enzyme was thus confirmed to be chloramphenicol acetyltransferase. The enzyme was inducible. It was partially purified by ammonium sulfate precipitation, DEAE-cellulose chromatography and gel filtration on Sephadex G-150. The enzymes obtained from S. haemolyticus, S. pneumoniae and S. faecalis have been compared with the conclusion that they are identical with respect to molecular weight (approximately 75,000-80,000), optimum pH and heat stability.
Fifty clinical isolates of Streptococcus pneumoniae received by the Streptococcus Laboratory of the Center for Disease Control from August 1976 through March 1977 and 50 pneumococcal strains retrieved from 13- to 16-year storage (originally isolated October 1961 through December 1964) were tested for susceptibility to 10 antimicrobial agents by disk-agar diffusion and agar dilution tests. No appreciable differences in susceptibility patterns were apparent between the two groups, and, except for one isolate, all were highly susceptible to every drug tested except gentamicin. This single isolate required higher drug concentrations to inhibit macroscopic growth and had corresponding decrements in zones of disk inhibition with penicillin, ampicillin, and cephalothin. An additional 43 pneumococci recently received from various areas of the United States and Canada were screened by a disk agar diffusion method for penicillin resistance. Four of these isolates had penicillin zone diameters <30 mm, and subsequent agar dilution test results showed that the penicillin minimum inhibitory concentrations were elevated with these organisms. Antimicrobial susceptibility patterns of pneumococci to antimicrobials other than penicillin and its analogs have not changed substantially in over a decade. However, due to the emergence of strains with decreased susceptibility to penicillin, the screening test for penicillin resistance in pneumococci, especially in isolates from spinal fluid and blood, could be clinically useful as an aid in selecting optimal therapy.
UNLABELLED: Streptococcus pneumoniae causes significant morbidity and mortality worldwide, and serotyping is important to assess the burden of disease that is vaccine preventable. For serotyping, the Centers for Disease Control and Prevention (CDC) use a series of 12 real-time multiplex PCRs (rmPCRs) performed in quadruplex reactions; however, rmPCR reaction 5 (rmPCR-5) for serotypes 6A, 6B, 6C, and 6D often failed at low DNA concentrations. This study investigated the cause of rmPCR-5 failure and provided alternative rmPCRs to resolve this issue. Quadruplex rmPCR target sequences were compared to S. pneumoniae reference genomes. Reactions rmPCR-5 [6ABCD, 6AB, 6BD, and 6CD] and rm-PCR-11 [37, 10F, 11BC, and 18CFBA] were compared to alternative reactions rmPCR-A1 [6ABCD, 10F, 11BC, and 18CFBA] and rmPCR-A2 [37, 6AB, 6BD, and 6CD]. All rmPCRs were tested using 10-fold serial dilutions of DNA from representative serotypes, and analytical specificity was assessed using DNA from other S. pneumoniae serotypes or various streptococci and Gram-positive cocci. Failure of rmPCR-5 was associated with overlapping 6ABCD and 6BD targets. Separation of these targets in the alternative rmPCRs-A1 and rmPCR-A2 allowed sensitive and specific detection and discrimination of serotypes 6A, 6B, 6C, and 6D, without impacting the detection of serotypes 10F, 11BC, 18CFBA, and 37. This study highlights the importance of rigorous author and peer-review to avoid manuscript errors and unintended consequences. By explaining what caused rmPCR-5 failure and proposing alternative reactions rmPCRs-A1 and rmPCR-A2, this study demonstrates the value of scientific collaboration to ensure molecular assays best serve the scientific community. IMPORTANCE: Streptococcus pneumoniae is a bacterium that can cause life-threatening infections like pneumonia and meningitis, leading to millions of deaths worldwide each year. A key feature enabling S. pneumoniae to cause disease is its sugar coating, allowing it to avoid the immune system. These surface sugars are the target of S. pneumoniae vaccines. However, vaccines only protect against some sugars and understanding which ones are on the surface of S. pneumoniae is called "serotyping." The Centers for Disease Control and Prevention (CDC) have protocols that allow us to predict S. pneumoniae serotypes by looking at its DNA. We found errors in the CDC protocols and provided a simple solution to fix them. Ultimately, having accurate serotyping protocols allows us to know how much disease is preventable by vaccine, allows us to monitor how well vaccine are working, and helps develop new vaccines if needed.
The isolation rate of Streptococcus pneumoniae in sputum cultures from patients with pneumococcal pneumonia is low. An investigation was made to determine whether this low yield might be due to loss of pneumocci and/or overgrowth by pharyngeal flora before the specimen is plated. Pneumococcal survival times and pharyngeal overgrowth at 4 degrees C and at room temperature were determined in sputum obtained from 42 patients with pneumococcal pneumonia. It was found that pneumococci survived for long periods in sputum--2.2 +/- 1.4 days at room temperature and 9.5 +/- 3.6 days at 4 degrees C. Overgrowth by pharyngeal flora occurred in only 6 of 42 specimens kept at 4 degrees C and 31 of 42 specimens kept at room temperature. The low yield of S. pneumoniae in sputum from patients with pneumococcal pneumonia is not explained by decreased viability of the organism.
A previously healthy 23-year-old white woman had fulminant pneumococcal pneumonia complicated by empyema and bilateral pneumothoraces. Despite early treatment with the recommended doses of minocycline, the disease progressed. The S pneumoniae isolate was resistant to a 30microgram tetracycline disk and showed an MIC of 3.13microgram/ml for minocycline and 12.5 microgram/ml for tetracycline; these levels are considered by the manufacturer to indicate sensitivity to minocycline and intermediate sensitivity to tetracycline. The tetracyclines, including minocycline, should not be used to treat bacterial pneumonia since resistant strains of pneumococci are not uncommon and inffective treatment can lead to rapid progression of the infection. This case suggests that the levels of minocycline considered to indicate sensitivity in vitro be reassessed.
Serotypes of Streptococcus pneumoniae from 525 infected children were examined over a four-year period. Type distribution was similar among 84 cases of bacteremia and 30 cases of meningitis, with types 6, 14, and 18 accounting for half of the illnesses. In contrast, half of 396 episodes of otitis media were caused by three other types, 19, 23, and 3. Four of eight fatalities were due to type 6. Carrier strains isolated from children had a distribution of types similar to that of the otitis media collection. Adult patients had fewer of the types that caused disease in children. Most childhood infections (80%) occurred in children less than or equal to 24 months of age; no relationship between age and infecting serotype was noted. There were no seasonal trends in type distribution.
Streptococcus pneumoniae (pneumococcus) is a leading cause of community-acquired pneumonia and invasive diseases, particularly among children and the elderly. The introduction of pneumococcal conjugate vaccines has significantly reduced invasive pneumococcal disease, but the prevalence of non-vaccine serotypes and newly emerging serotypes is increasing globally. Thus, accurate serotyping is essential for epidemiological surveillance and the development of next-generation multivalent pneumococcal vaccines. Conventional serotyping methods, including multiplex polymerase chain reaction (mPCR), monoclonal antibody (mAb) assays, and Quellung reaction using rabbit antisera, are limited by serotype coverage and cross-reactivity, making the detection of new or emerging serotypes challenging. In this study, we developed a nanopore Cas9-targeted serotyping (nCATSerotyping) platform, which employs Cas9-mediated enrichment of the capsular polysaccharide synthesis locus followed by Oxford Nanopore sequencing. Applying this method to 276 clinical pneumococcal isolates collected in South Korea (2018-2020), we achieved a serotyping success rate of 97.10% (268/276), significantly outperforming conventional methods such as mAb and mPCR, which identified only 76.45% (211/276) of isolates. Whole-genome sequencing of the remaining eight non-typeable isolates revealed them to be non-pneumococcal (oral streptococci), confirming 100% accuracy for S. pneumoniae serotyping. Importantly, our method identified emerging and underrepresented serotypes, including serotype 13 and null capsule clade strains. nCATSerotyping offers a rapid, accurate, and comprehensive solution for pneumococcal serotyping, with significant advantages in identifying novel and non-typeable strains. This scalable platform will be a valuable tool for global serotype surveillance and next-generation multivalent pneumococcal vaccine development.IMPORTANCEAccurate pneumococcal serotyping is critical for vaccine development and epidemiological surveillance, particularly as non-vaccine serotypes emerge following widespread pneumococcal conjugate vaccine implementation. Current serotyping methods face significant limitations in coverage and accuracy, identifying around 76% of pneumococcal isolates and failing to detect emerging serotypes like serotype 13 and null capsule clades. The nanopore Cas9-targeted serotyping platform addresses these critical gaps by achieving 100% serotyping accuracy for confirmed Streptococcus pneumoniae isolates while identifying previously undetectable strains that conventional methods missed. This comprehensive approach is essential for monitoring vaccine effectiveness, understanding serotype replacement patterns, and informing next-generation vaccine development strategies. Furthermore, the identification of misclassified oral streptococci highlights the diagnostic precision needed for accurate pneumococcal surveillance, ensuring that epidemiological data accurately reflect true pneumococcal disease burden and serotype distribution patterns.
Six of 36 strains of Streptococcus pneumoniae isolated in our laboratory during 1977 showed relative resistance to penicillin G. This level of resistance was detectable only by the broth dilution method. Using the disk diffusion method, all six strains appeared susceptible (zone size > 29 mm).
After exposure of type I Streptococcus pneumoniae to nitrosoguanidine, 13 temperature-sensitive (ts) mutants were selected that were restricted in capacity to form colonies on blood agar at 38 C. Whereas colony formation by the type I parent (ts+) was unaffected by a temperature of as high as 39 C, the ts mutants exhibited a spectrum of temperature sensitivity in which colony formation was inhibited significantly at 36 C, 37 C, 38 C, or 39 C. Growth of ts mutants at 38 C in broth was reduced or delayed relative to that of ts organisms under identical conditions. In general, there was a direct correlation between degree of temperature sensitivity and genetic stability. Mutants grown at a permissive temperature resembled the ts+ type I parent in colonial morphology and properties of alpha-hemolysis, bile solubility, optochin sensitivity, and antibiotic sensitivity. Moreover, in vitro studies indicated that the mutants retained capsules of immunochemically reactive type I capsular polysaccharide.
Bacterial strains of Haemophilus species and Streptococcus pneumoniae were examined for synthesis of the enzyme immunoglobulin A1 (IgA1) protease. Of 36 H. influenzae strains examined, 35 produced IgA1 protease; strains included all six capsular types, unencapsulated variants of types b and d, and untypable H. influenzae. Eight Haemophilus strains (non-H. influenzae) were studied, and two produced IgA1 protease. All 10 strains of S. pneumoniae produced IgA1 protease; these strains included 9 different capsular polysaccharide types and 1 untypable strain. Both IgA1 proteases cleaved myeloma IgA1 and secretory IgA but not myeloma IgA2, IgM, or IgG as determined by immunoelectrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that both enzymes cleaved IgA1 myeloma sera, but not IgA2, into two fragments. The apparent molecular weight of the cleaved fragments was dependent both on the apparent molecular weight of the cleaved fragments was dependent both on the specific IgA1 protease assayed and the specific IgA1 substrate utilized. It is postulated that both carbohydrate variation between the IgA1 substrates studied and the ability of S. pneumoniae glycosidases to cleave carbohydrates from glycoprotein offer an explanation for the different fragment sizes observed.
Over eight months 130 isolates of Streptococcus pneumoniae were examined for sensitivity to penicillin, tetracycline, cephalosporin and co-trimoxozole. Except in one doubtful case all isolates were sensitive to penicillin. All were sensitive to cephalosporin. 6.9 percent is isolates were resistant to co-trimoxozole. It is suggested that penicillin remains the drug of choice in the treatment of pneumococcal infections.
Competence is an important bioprocess for Streptococcus pneumoniae. Previously, we demonstrated that the bacterial second messenger cyclic di-adenosine monophosphate (c-di-AMP) modulates pneumococcal competence. Surprisingly, cdaA*, a strain producing less c-di-AMP due to a point mutation in the diadenylate cyclase CdaA, is susceptible to competence-stimulating peptide (CSP). In this study, we screened cdaA* suppressor mutants resistant to CSP to explore the underlying mechanism. Of 14 clones sequenced, nine clones possessed mutations in the c-di-AMP phosphodiesterase Pde1, indicating that the susceptibility to CSP of the cdaA* strain is correlated to c-di-AMP levels. Another two clones exhibited a mutation in FabT, a transcription factor controlling cell membrane fatty acid biosynthesis. We further showed that deletion of fabT, disruption of the FabT-binding site within the PfabK promoter, deletion of a fabT activator BriC, or disruption of K+ uptake in the cdaA* mutant all rescued the growth defect of the cdaA* strain in media supplemented with CSP. Finally, we found that a c-di-AMP phosphodiesterase-null mutant with high levels of c-di-AMP is highly sensitive to treatment with either ethanol or Triton X-100, which could be corrected by reducing c-di-AMP levels through introducing point mutations in CdaA. Together, these findings indicate that c-di-AMP affects cell membrane integrity.
Among 40 fresh isolates of Streptococcus pneumoniae 12, 25 and 3 strains, respectively, exhibited large round, small round and compact colonial morphologies in soft-agar medium. Every large round strain possessed a capsule, almost half of the small round strains had capsules, while all of the large round type growth showed very high mouse virulence and 1.0 mg of these organisms was capable of absorbing a minimal amount of passive protective antibody in rabbit antiserum, prepared with the homologous strain, against challenge infection with homologous organisms in mice. Its variant showing compact type growth in soft-agar was mouse avirulent and a similar amount of the mouse passive protective antibody could not be absorbed with 100 mg of these organisms. These experimental results indicate that the soft-agar technique can be used for the identification of encapsulated strains of Streptococcus pneumoniae.
Streptococcus pneumoniae (Spn) asymptomatically colonizes the upper respiratory tract (URT), a niche from which it can transmit to another host or cause invasive disease in the same host. The in vivo transcriptional adaptations that Spn undergoes during nasopharyngeal colonization, particularly during influenza A virus (IAV) co-infection, are poorly understood. Here, we leveraged an established infant mouse model of colonization, shedding, and transmission to perform genome-wide transcriptomic profiling of Spn during mono- and during IAV co-infection. Compared with broth-grown controls, pneumococci isolated from the URT exhibited distinct transcriptional programs, with over 200 genes differentially expressed across time points. Genes involved in carbohydrate uptake and metabolism, glycan degradation, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were consistently enriched during colonization, highlighting metabolic adaptation to the nasopharyngeal niche. In contrast, IAV co-infection induced a markedly distinct transcriptional signature, including upregulation of branched-chain amino acid biosynthesis, bacteriocin production, and phosphate acquisition systems. Notably, the pilus islet-1 locus was upregulated during Spn-IAV co-infection. Functional studies demonstrated that while the pilus was dispensable for colonization under mono- and co-infection conditions, it promoted high-shedding events and enhanced inflammatory responses during IAV co-infection. However, reduced inflammation and reduced high-shedding events from pups inoculated with a pilus-deficient mutant did not alter transmission frequency in the infant mouse model. Collectively, our findings define the in vivo transcriptional landscape of Spn during URT colonization and reveal distinct bacterial adaptations during viral co-infection, providing insight into mechanisms that influence pneumococcal persistence, inflammation, and transmission.
An obligately anaerobic strain of Streptococcus pneumoniae was isolated from blood culture in a 14-month-old child with an upper respiratory tract infection.
Ninety-seven isolates of Streptococcus pneumoniae referred to the National Health Institute between January 1976 and March 1978 were tested for their susceptibility to 10 antimicrobials. All were susceptible to penicillin, erythromycin, chloramphenicol, vancomycin, clindamycin, cephalothin and rifampicin. Resistance to tetracycline was found in 9.3 percent of the isolates, and 9.7 percent were resistant to a combination of sulphamethoxazole and trimethoprim.
It was possible to transfect Streptococcus pneumoniae with DNA obtained from a newly isolated bacteriophage, diplophage-4 (Dp-4). Optimal frequency of transfection (0.9%) required the use of a nuclease-defective mutant; with wild-type bacteria, the transfection frequency was about 100-fold lower. Transfection requires physiological conditions that appear to be similar to the competent state needed for genetic transformation (A. Tomasz, J. Bacteriol. 91:1050--1061, 1966).