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- Carlsson Wistedt, Annika
(författare)
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Plasminogen and protein PAM: Interactions between streptococcal surface proteins and the human fibrinolytic system
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pathogenic bacteria often produce potent proteases capable of destroying host tissue thereby providing the bacteria with tools for spreading and nutrient access. This thesis describes how group A, C and G streptococci can acquire surface bound protease activity through an alternative mechanism, namely by binding and activation of the human protease precursor plasminogen. Group A streptococci of certain serotypes (M33, M41, M52, M53 and M56) were found to efficiently bind plasminogen. Similar to a previously described protein (PAM) expressed by a M53 strain, the plasminogen-binding surface proteins of the other four serotypes belonged to the M protein family, known to contain major virulence factors of group A streptococci. In addition, a subset of group C and G streptococci were shown to bind plasminogen through M-like proteins. In binding experiments with recombinantly produced fragments and a synthetic pepide we located the plasminogen-binding site of protein PAM to a 29 amino acid region containing a twice-repeated sequence. Two lysine residues within this sequence appeared to be critical for the interaction with plasminogen. The major binding site for PAM to plasminogen was localised to kringle two of human plasminogen. PAM reacted poorly with plasminogen from some other species, including rheusus plasminogen which only differs from the human form in two positions. PAM-expressing bacteria grown in human plasma acquired surface associated plasmin activiy in spite of the presence of physiological plasmin inhibitors. A chimerical M-like protein, harbouring the plasminogen-binding motif of PAM, transferred this ability to another streptococcal strain. Inactivation of the streptokinase gene abolished surface plasmin acquisition whereas addítion of exogenous streptokinase overcame this block.
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| 2. |
- Lindqvist, Maria, et al.
(författare)
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Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.
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