Global Effects of Catecholamines on Actinobacillus pleuropneumoniae Gene Expression

Bacteria can use mammalian hormones to modulate pathogenic processes that play essential roles in disease development. Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen causing great economic losses in the pig industry globally. Stress is known to contribute to the outcome of A. pleuropneumoniae infection. To test whether A. pleuropneumoniae could respond to stress hormone catecholamines, gene expression profiles after epinephrine (Epi) and norepinephrine (NE) treatment were compared with those from untreated bacteria. The microarray results showed that 158 and 105 genes were differentially expressed in the presence of Epi and NE, respectively. These genes were assigned to various functional categories including many virulence factors. Only 18 genes were regulated by both hormones. These genes included apxIA (the ApxI toxin structural gene), pgaB (involved in biofilm formation), APL_0443 (an autotransporter adhesin) and genes encoding potential hormone receptors such as tyrP2, the ygiY-ygiX (qseC-qseB) operon and narQ-narP (involved in nitrate metabolism). Further investigations demonstrated that cytotoxic activity was enhanced by Epi but repressed by NE in accordance with apxIA gene expression changes. Biofilm formation was not affected by either of the two hormones despite pgaB expression being affected. Adhesion to host cells was induced by NE but not by Epi, suggesting that the hormones affect other putative adhesins in addition to APL_0443. This study revealed that A. pleuropneumoniae gene expression, including those encoding virulence factors, was altered in response to both catecholamines. The differential regulation of A. pleuropneumoniae gene expression by the two hormones suggests that this pathogen may have multiple responsive systems for the two catecholamines

Fatal injuries while under the influence of psychoactive drugs: a cross-sectional exploratory study in England

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: Studies of drug-related mortality rarely describe fatal injuries due to psychoactive drug intoxication (FIUI). The main aim of this study was to determine the nature, extent and pattern of FIUI. METHODS: This observational study covered the period January 1999 to December 2001. Data were provided by members of a study panel of coroners in England using a standard protocol. Sources of data for this study included autopsy protocols, death certificates, hospital records, police reports, toxicology reports and inquest transcripts. Inclusion criteria for this were (i) the mention of one or more psychoactive substances as contributing to fatality; and (ii) the presence of a Controlled Drug at post mortem. RESULTS: A total of 3,803 drug-related deaths of persons aged 16-64 years were reported by the study panel during the three-year period. The study panel accounted for 86% of drug-related deaths in England in this period. There were 147 FIUI cases (119 males, 28 females), giving a proportionate mortality ratio of approximately 4%. The majority of FIUI cases (84%) were aged 16-44 years, with a median age at death of 33 years (Quartile deviation = 7). Fifty-six percent of FIUI occurred in urban areas of England. The population of the study jurisdictions aged 16-64 years contributed 49,545,766 person-years (py) to the study, giving an annual crude rate of 3/1,000,000 person-years (py). Rates for male and females were 4.9 and 1.1/1,000,000 py respectively, giving a male/female rate ratio of 4.5 (95%CI = 2.9-6.8). The rates of intentional and unintentional FIUI were 2 and 1/1,000,000 py respectively. The leading mechanism for intentional FIUI was suffocation while the predominant mechanisms in unintentional FIUI were road traffic accidents and falls. There is a significant difference in the pattern of drug-specific risk between FIUI and fatal poisoning. Risks of intentional FIUI are elevated among Black and Minority Ethnic groups. CONCLUSION: There are differences in the nature, extent and pattern of intentional and unintentional FIUI that should necessitate targeted prevention strategies. Also, there is an opportunity for cross-discipline collaboration between injury prevention specialists and substance abuse/mental health specialists.Peer reviewedFinal Published versio