Streptococcus gallolyticus - A potentially neglected pathogen causing neonatal sepsis not covered by routine group B streptococcus screening.

We report 4 cases of neonatal sepsis caused by Streptococcus gallolyticus. The clinical course was quite similar to early-and late-onset group B streptococcus disease. None of the mothers had group B streptococcus (GBS) colonization on prenatal screening nor received intrapartum antibiotics. We proposed the sporadic distribution of S. gallolyticus sepsis among neonates was partly due to relatively low colonization rate in adults compared with GBS. Species determination of S. gallolyticus may not be available using conventional microbiological methods and may contribute to underestimation or misclassification. In our series, we highlighted the importance of S. gallolyticus as an important pathogen in neonatal sepsis deserving further surveillance.

Microbiological and clinical characteristics of Streptococcus gallolyticus subsp. pasteurianus infection in China.

BACKGROUND: Infections by Streptococcus gallolyticus subsp. pasteurianus (SGSP) is often underestimated. Herein, the epidemiological features and resistant characteristics of SGSP in mainland China are characterized to enable a better understanding of its role in clinical infections. METHODS: In the present work, 45 SGSP isolates were collected from the samples of bloodstream, urine, aseptic body fluid, and fetal membrane/placenta from patients in 8 tertiary general hospitals of 6 cities/provinces in China from 2011 to 2017. The identification of all isolates was performed using traditional biochemical methods, 16S rRNA and gyrB sequencing, followed by the characterization of their antibiotic resistance profiling and involved genes. RESULTS: Among 34 non-pregnancy-related patients, 4 (4/34,11.8%) patients had gastrointestinal cancer, 10 (10/34, 29.4%) patients had diabetes, and one patient had infective endocarditis. Moreover, 11 cases of pregnant women were associated with intrauterine infection (9/11, 81.2%) and urinary tract infection (1/11, 9.1%), respectively. Except one, all other SGSP isolates were correctly identified by the BD Phoenix automated system. We found that all SGSP isolates were phenotypically susceptible to penicillin, ampicillin, cefotaxime, meropenem, and vancomycin. Forty strains (40/45, 88.9%) were both erythromycin and clindamycin-resistant, belonging to the cMLSB phenotype, and the majority of them carried erm(B) gene (39/40, 97.5%). Although the cMLSB/erm(B) constituted the most frequently identified phenotype/genotype combination (25/40, 62.5%) among all erythromycin-resistant cMLSB isolates, erm(B)/erm(A), erm(B)/mef(A/E), and erm(B)/erm(T) was detected in 7, 4, and 3 isolates, respectively. Furthermore, 43 strains (43/45, 95.6%) were tetracycline-resistant, and out of these, 39 strains (39/45, 86.7%) carried tet(L), 27(27/45, 60.0%) strains carried tet(O), and 7 (7/45, 15.6%) strains carried tet(M), alone or combined, respectively. All erythromycin-resistant isolates were also resistant to tetracycline. CONCLUSIONS: It is important to study and draw attention on SGSP, an underreported opportunistic pathogen targeting immunodeficient populations, notably elderly subjects, pregnant women and neonates.

Characterization of Erythromycin and Tetracycline Resistance Genes of Streptococcus gallolyticus Subspecies pasteurianus Strains Isolated from Patients with Septicemia and Bacteremia in Thailand.

BACKGROUND: Streptococcus gallolyticus subspecies (subsp.) pasteurianus, previously known as Streptococcus bovis biotype II/2, has been described as a causative agent of endocarditis, neonatal sepsis, meningitis, bacteremia, and colorectal carcinoma in humans. The aim of this study was to characterize the erythromycin and tetracycline resistance genes of S. gallolyticus subsp. pasteurianus strains isolated from patients with septicemia and bacteremia in Thailand. METHODS: The clinical isolates of Streptococcus gallolyticus were identified by using conventional biochemical tests, PCR, and sodA gene sequence analysis. The erythromycin and tetracycline susceptibilities were determined by disk diffusion and agar dilution methods, while the resistance genes were identified by nucleotide sequence analysis. RESULTS: From a total of 108 blood cultures, 36 (33%) were identified as S. gallolyticus subsp. pasteurianus with the nucleotide sequence identities of partial sodA gene with the reference strains ranging from 98.1 to 100%. Of these, 25 (69.4%) contained erythromycin resistance genes and erm(B) was the most predominant gene (30.6%), followed by erm(T) (19.4%) and mef(A) (5.6%). In addition, erm(B) was also detected in combination with lnu(B) (8.3%), erm(T) and mef(A) (2.8%), and mef(A) and lnu(B) (2.8%). It was interesting to note that lnu(B) was detected for the first time in S. gallolyticus subsp. pasteurianus in this study. For tetracycline resistance genes, tet(L) and tet(M) were detected at 13.9% and 11.1%, respectively. However, tet(M) in combination with tet(L) was detected most commonly at 69.4% and with tet(L) and tet(O) at 5.6%. CONCLUSIONS: A number of erythromycin and tetracycline resistance genes were detected in S. gallolyticus subsp. pasteurianus strains circulating in Thailand.

Novel Tn916-like elements confer aminoglycoside/macrolide co-resistance in clinical isolates of Streptococcus gallolyticus ssp. gallolyticus.

Background: Streptococcus gallolyticus ssp. gallolyticus (Sgg) is a commensal bacterium and an opportunistic pathogen. In humans it has been clinically associated with the incidence of colorectal cancer (CRC) and epidemiologically recognized as an emerging cause of infective endocarditis (IE). The standard therapy of Sgg includes the administration of a penicillin in combination with an aminoglycoside. Even though penicillin-resistant isolates have still not been reported, epidemiological studies have shown that this microbe is a reservoir of multiple acquired genes, conferring resistance to tetracyclines, aminoglycosides, macrolides and glycopeptides. However, the underlying antibiotic resistance mobilome of Sgg remains poorly understood. Objectives: To investigate the mobile genetic basis of antibiotic resistance in multiresistant clinical Sgg. Methods: Isolate NTS31106099 was recovered from a patient with IE and CRC at Nantes University Hospital, France and studied by Illumina WGS and comparative genomics. Molecular epidemiology of the identified mobile element(s) was performed using antibiotic susceptibility testing (AST), PCR, PFGE and WGS. Mobility was investigated by PCR and filter mating. Results: Two novel conjugative transposons, Tn6263 and Tn6331, confer aminoglycoside/macrolide co-resistance in clinical Sgg. They display classical family Tn916/Tn1545 modular architecture and harbour an aph(3')-III→sat4→ant(6)-Ia→erm(B) multiresistance gene cluster, related to pRE25 of Enterococcus faecium. These and/or closely related elements are highly prevalent among genetically heterogeneous clinical isolates of Sgg. Conclusions: Previously unknown Tn916-like mobile genetic elements conferring aminoglycoside/macrolide co-resistance make Sgg, collectively with other gut Firmicutes such as enterococci and eubacteria, a potential laterally active reservoir of these antibiotic resistance determinants among the mammalian gastrointestinal microbiota.

Identification, antimicrobial resistance and molecular characterization of the human emerging pathogen Streptococcus gallolyticus subsp. pasteurianus.

This study aimed to retrospectively identify 22Streptococcus bovis clinical strains based on the new taxonomy, as well as to investigate their antibiotic-resistance and clonality. Strains were identified by Phoenix100 system, 16S rRNA sequencing, and two MALDI-TOF MS platforms (Bruker Biotyper, Vitek MS). Antibiotic resistance was determined both phenotypically and genotypically, and clonality was assessed by PFGE. Most of strains (63.6%) were isolated from urine, and diabetes was the most common underlying disease (31.8%). Phoenix100 system revealed all strains belonged to biotype II, and 16S rRNA sequencing identified all strains as S. gallolyticus subsp pasteurianus (SGSP). Although both MALDI-TOF MS systems correctly identified isolates to the species level, only Bruker Biotyper accurately identified to the subspecies level. Erythromycin-resistant strains (31.8%) were also clindamycin-resistant and positive for erm(B). Strains resistant to tetracycline (68.2%) were also resistant to erythromycin. PFGE showed high genetic variability identifying 17 different pulsotypes, most of which single.

Inducible Expression of both ermB and ermT Conferred High Macrolide Resistance in Streptococcus gallolyticus subsp. pasteurianus Isolates in China.

Streptococcus gallolyticus subsp. pasteurianus is an under-recognized pathogen and zoonotic agent causing opportunistic infections in humans. Despite increasing recognition of this subspecies as a cause for human infectious diseases, limited information is known about its antibiotic resistance mechanism. In this study, we aim to identify the molecular mechanism underlying the high macrolide resistance of six S. gallolyticus subsp. pasteurianus isolates from dead ducklings collected in several natural outbreaks in China during 2010-2013. All isolates exhibited multi-drug resistance including high macrolide resistance (MIC ≥ 1024 mg/L for erythromycin, and 512 mg/L for clarithromycin). Efflux-encoding mefA and mefE genes were not detectable in these isolates. The presence of 23S rRNA mutations in specific isolates did not significantly change macrolide MICs. No nucleotide substitutions were found in genes encoding ribosomal proteins L4 or L22. The ermB and ermT genes were found in the genomes of all isolates. These two genes were acquired independently in one highly virulent isolate AL101002, and clustered with Tn916 and IS1216, respectively. The expression of both ermB and ermT in all isolates was erythromycin inducible and yielded comparable macrolide MICs in all six isolates. Taken together, inducible expression of both ermB and ermT conferred high macrolide resistance in these S. gallolyticus subsp. pasterianus isolates. Our findings reveal new macrolide resistance features in S. gallolyticus subsp. pasteurianus by both ermB and ermT.