Clinical and molecular studies of β-haemolytic streptococci

Kristina Trell

Research output: ThesisDoctoral Thesis (compilation)

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Abstract

Beta-haemolytic streptococci (BHS) are important causes of human infections and they have traditionally been grouped according to Lancefield antigens. The spectrum of infections caused by BHS includes pharyngitis, skin infections, bacteraemia/sepsis, endocarditis, septic arthritis and meningitis. The most studied BHS is the group A Streptococcus (GAS), which concurs with the species Streptococcus pyogenes (SP). In the last decades, several studies have shown an increase of invasive infections caused by beta-haemolytic streptococci group C (GCS) and group G (GGS). GCS and GGS cause clinical disease similar to GAS. The vast majority of clinical isolates associated with human infections, that are identified as GCS and GGS belong to the species Streptococcus dysgalactiae (SD). With the introduction of Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) in routine diagnostics, it became possible to determine species of GGS and GCS. GCS and GGS exhibit the M-protein, a known virulence factor in GAS infections. The M-protein is encoded by the emm-gene and sequencing of this gene can be used for typing purposes.

In the first study, isolates of GCS and GGS from different sites of isolation (throat, wound, and blood) was species determined and emm-typed to investigate if certain types have a predilection to cause particular infections. We found that GCS and GGS express different emm-types and that GCS and GGS from different sites of isolation were similar, suggesting that emm-types are not associated to certain disease presentations.

In the second study, subjects with recurrent bacteraemia with GCS and GGS were identified and compared to controls with only one episode of bacteraemia to detect risk factors for recurrence. In the 23 patients with recurrent episodes of SD bacteraemia, most recurrences were caused by the same emm-type suggesting a host-specific colonization. In addition, no specific emm-types or other clinical factors were significantly associated with recurrences.

Among GCS causing human infections, isolates of Streptococcus equi (SE) have been found. In the third study, the clinical course of patients with bacteraemia with SE were described and the isolates were typed through sequencing of the gene encoding the M-like protein SzP. Eighteen cases of SE were found during a thirteen-year period, which confirms that SE is a rare cause of infection in humans. No temporal or geographical clustering was found in our material. Our study also indicated that sporadic cases of SE bacteraemia have a favourable
prognosis.

In the fourth work, we investigated the possibility of using cultures for diagnostic purposes by determining the perianal colonization with BHS in patients with erysipelas compared with a control group. In the group with erysipelas, 44% of the patients were colonized with BHS compared with 4 % of the patients in the control group. The BHS found were most commonly GGS and when subjected to MALDI-TOF MS, these were found to be SD. We concluded that SD colonizes the perianal area in a substantial proportion of patients with erysipelas.

SP is a well-known cause of postpartum infections and is still causing significant morbidity and mortality worldwide. In the final study, we described the use of whole genome sequencing (WGS) to investigate an outbreak of postpartum SP emm75 infections related to an asymptomatic carrier working in a maternity ward. Source identification and WGS proved to be vital for outbreak control.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Clinical Sciences, Lund
Supervisors/Advisors
  • Rasmussen, Magnus, Supervisor
  • Nilson, Bo, Assistant supervisor
Award date2019 Nov 15
Place of PublicationLund
Publisher
ISBN (Print)978-91-7619-840-7
Publication statusPublished - 2019

Bibliographical note

Defence details
Date: 2019-11-15
Time: 09:00
Place: Belfragesalen, BMC D15, Klinikgatan 32 i Lund
External reviewer:
Name: Skrede, Steinar
Title: Professor
Affiliation: Department of Clinical Science, University of Bergen, Norway.

Subject classification (UKÄ)

  • Infectious Medicine

Free keywords

  • Beta-hemolytic streptococci
  • Streptococcus dysgalactiae
  • MALDI-TOF MS analysis
  • Streptococcus equi
  • Streptococcus pyogenes
  • endometritis
  • Erysipelas

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