Heat Resistance Mediated by a New Plasmid Encoded Clp ATPase, ClpK, as a Possible Novel Mechanism for Nosocomial Persistence of Klebsiella pneumoniae

Klebsiella pneumoniae is an important opportunistic pathogen and a frequent cause of nosocomial infections. We have characterized a K. pneumoniae strain responsible for a series of critical infections in an intensive care unit over a two-year period. The strain was found to be remarkably thermotolerant providing a conceivable explanation of its persistence in the hospital environment. This marked phenotype is mediated by a novel type of Clp ATPase, designated ClpK. The clpK gene is encoded by a conjugative plasmid and we find that the clpK gene alone renders an otherwise sensitive E. coli strain resistant to lethal heat shock. Furthermore, one third of a collection of nosocomial K. pneumoniae isolates carry clpK and exhibit a heat resistant phenotype. The discovery of ClpK as a plasmid encoded factor and its profound impact on thermal stress survival sheds new light on the biological relevance of Clp ATPases in acquired environmental fitness and highlights the challenges of mobile genetic elements in fighting nosocomial infections

Low-dose methamphetamine addiction induced opioid receptor sensitization in polydrug-dependent mice

Polydrug dependence shows an increasing trend in prevalence among addicts. It is a result of an addict abusing another drug to mask the undesirable effects of another drug. However, this could lead to adverse neuroadaptations. Therefore, we aim to investigate the effects of low-dose methamphetamine use in morphine-dependent subjects during reinstatement following treatment (0.3 mg/kg buprenorphine / 1.0 mg/kg naltrexone combination) in mice. Using tail-withdrawal assay, the involvement of opioid receptors was investigated at 1.0-5.0 mg/kg methamphetamine, i.p. at 52°C. The results showed that analgesic activity was only detected at the highest dose given which was successfully blocked with 1.0 mg/kg naltrexone, i.p. (p45°) which was not detected in the morphine-, methamphetamine-dependent groups and during pre-screening of treatment drug. This suggest that although methamphetamine has little apparent withdrawal symptoms, it has the ability to sensitize the opioid receptors even at 'inactive' dose when it is used concurrently with morphine

Role of opioid receptors in the reinstatement of opioid-seeking behavior: an overview

Opioid abuse in humans is characterized by discontinuous periods of drug use and abstinence. With time, the probability of falling into renewed drug consumption becomes particularly high and constitutes a considerable problem in the management of heroin addicts. The major problem in the treatment of opioid dependence still remains the occurrence of relapse, to which stressful life events, renewed use of heroin, and exposure to drug-associated environmental cues are all positively correlated. To study the neurobiology of relapse, many research groups currently use the reinstatement animal model, which greatly contributed to disentangle the mechanisms underlying relapse to drug-seeking in laboratory animals. The use of this model is becoming increasingly popular worldwide, and new versions have been recently developed to better appreciate the differential contribution of each opioid receptor subtype to the relapse phenomenon. In this chapter we review the state of the art of our knowledge on the specific role of the opioid receptors as unrevealed by the reinstatement animal model of opioid-seeking behavior