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The three different pore-forming RTX-toxins of Actinobacillus pleuropneumoniae are reviewed, and new and uniform designations for these toxins and their genes are proposed. The designation ApxI (for &tinobacillus pZeuropneumoniae RTX-toxin I) is proposed for the RTX-toxin produced by the reference strains for serotypes 1, 5a, 5b, 9,lO and 11, which was previously named haemolysin I (HlyI) or cytolysin I (ClyI). This protein is strongly haemolytic and shows strong cytotoxic activity towards pig alveolar macrophages and neutrophils; it has an apparent molecular mass in the range 105 to 110 kDa. The genes of the apxZ operon will have the designations apxZC, apxZA, apxZB, and apxZD for the activator, the structural gene and the two secretion genes respectively. The designation ApxII is proposed for the RTX-toxin which is produced by all serotype reference strains except serotype 10 and which was previously named App, HlyII, ClyII or Cyt. This protein is weakly haemolytic and moderately cytotoxic and has an apparent molecular m a s between 103 and 105 kDa. The genes of the apxZZ operon will have the designations apxZZC for the activator gene and apxZZA for the structural toxin gene. In the apxZZ operon, no genes for secretion proteins have been found. Secretion of ApxII seems to occur via the products of the secretion genes apxZB and apxZD of the apxZ operon. The designation ApxIII is proposed for the nonhaemolytic RTX-toxin of the reference strains for serotypes 2, 3, 4, 6 and 8, which was previously named cytolysin 111 (ClyIII), pleurotoxin (Ptx), or macrophage toxin (Mat). This protein is strongly cytotoxic and has an apparent molecular mass of 120 kDa. The genes of the apxZZZ operon have the designations apxZZZC, apxZZZA, apxZZZB and apxZZZD for the activator gene, the structural gene and the two secretion genes respectively.

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Actinobacillus pleuropneumoniae serotype reference strains and 204 A. pleuropneumoniae field strains representing all 12 serotypes and both biovars 1 and 2, obtained from laboratories from various countries worldwide, were analyzed for the presence of the toxin genes apxIC, apxIA, apxIB, apxID, apxIIC, apxIIA, apxIIIC, apxIIIA, apxIIIB, and apxIIID by DNA-DNA hybridization with specific gene probes. Expression of the toxins ApxI, ApxII, and ApxIII was assessed by immunoblot analysis with monoclonal antibodies. The results show that the patterns of apx genes and those of the expressed Apx toxins in biovar 1 field strains are the same as those of the genes and toxins of corresponding serotype reference strain. We found only three strains which had certain apx genes missing compared with the genes in their serotype reference strains. Analysis of the expression of the three toxins showed that nearly all strains expressed their apx genes and produced the same Apx toxins as their serotype reference strain. We found only one strain that did not produce ApxI, although it contained the apxICABD genes, and one strain which did not express ApxII but which contained apxIICA. Several field strains which initially showed that their serotype did not correspond to the apx gene profile of the reference strain and which had an unexpected virulence for the given serotype revealed that their initial serotyping was erroneous. We show that the apx gene profiles are inherent to a given serotype. The method cannot differentiate between all 12 serotypes. However, it allowed us to distinguish five groups of toxin gene patterns which showed pathological, toxicological, and epidemiological significance. None of the biovar 2 strains contained apxIII genes. The apxI and apxII genes in the biovar 2 strains, however, were the same as those found in the serotype reference strains of biovar 1.

A number of Escherichia coli strains have been isolated from dogs with urinary tract infections. These strains have been characterised with respect to their O, K, H, and fimbrial antigens, colicin production, antibiotic resistance, plasmid content and their ability to haemagglutinate erythrocytes from various species. Crossed immunoelectrophoresis of fimbrial extracts, as well as the reaction of partly purified fimbriae of a number of these strains with monoclonal antibodies revealed homology or a strong crossreaction with an F12 fimbrial subunit protein of human uropathogenic E. coli strains. Unlike human F12 fimbriae producing strains, the dog isolates did agglutinate dog erythrocytes in the presence of D-mannose but not human erythrocytes, indicating that the adhesin carried by these strains is different from the adhesin on fimbriae of human uropathogenic E. coli. Similar indications were obtained from experiments with latex beads coated with the receptor for P-fimbriae. These beads were agglutinated by Escherichia coli strains from human urinary tract infections, but not by the dog isolates described here. Preliminary adhesion experiments of human and dog Escherichia coli to human bladder epithelial and canine kidney epithelial cells also showed differences in adhesion depending on the origin of the strain tested.

SUMMARYThe virulence offaecal and urinary Escherichia coli strains was studied in relation to serotype, haemolysin production and haemagglutination pattern. By means of an experimental mouse model E. coli strains can be divided into avirulent (I), mouse nephropathogenic (II), and generally virulent (III) strains. Virulent group II and group III strains were more often haemolytic and haemagglutinating than avirulent group I strains. Presence of K antigen could not be associated with virulence. Discriminant analysis for qualitative variables revealed that no combination of the investigated properties contributed more to a strain's virulence level than did one single property. It is concluded that other virulence factors, apart from haemolysin production in group II strains and haemagglutinins in group III strains, must be involved in the determination of a strain's virulence level.All 02, 06 and 018 ac strains tested were virulent, and by far the most 075 strains were avirulent, whereas other 0 groups were more variable with regard to virulence. Pyelonephritis strains were more often mannose-resistant haemagglutinating than faecal and other urinary isolates, indicating that mannoseresistant adhesins may be important in the pathogenesis of pyelonephritis.

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In the context of increased pharmaceutical innovation deficits and Big Pharma blockbusters’ patent expirations, this paper examines the moderating role of firms’ absorptive capacity in external innovation activities of Big Pharma firms. The study indicates a rising interest of Big Pharma in acquisitions of and alliances with biotechnology companies. Unfortunately, this increased interest is not reflected in the number of new drugs generated by Big Pharma. We find that acquisitions of biotech companies have negatively affected Big Pharma firms’ innovation performance on average but these acquisitions might have a positive effect at higher levels of acquiring firms’ absorptive capacity. Moreover, also acquisitions of pharma companies and alliances with biotech companies only have a positive effect on innovation performance at sufficiently high levels of absorptive capacity. The moderating role of absorptive capacity implicates that a tight integration of internal R&D efforts and (unrelated) external knowledge is crucial for harnessing complementarity effects.