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Genetic Engineering of Clostridial Strains for Cancer Therapy
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Maria Zygouropoulou, Aleksandra Kubiak, Adam V. Patterson, Nigel P. Minton
In the case where the imaging functionality is introduced de novo into the clostridial vector, the options could extend beyond those discussed above. For fluorescence imaging, the clostridial host can be engineered to express oxygen-independent fluorescent proteins, which unlike the green fluorescent protein (GFP) do not require oxygen for chromophore maturation [120, 121]. For bioluminescence imaging, luminescence constructs such as the reshuffled luxABCDE operon optimized for expression in grampositive strains can be introduced in the clostridial host of interest [122]. Introduction of the entire operon would result in continuous luciferase-catalyzed light emission without the need of exogenous substrates, apart from molecular oxygen [123]. In the context of an anaerobic organism and the hypoxic environment of the tumor, the fulfillment of the oxygen requirement may pose a challenge. Nevertheless, it has been shown that the lux operon is functional even at very low oxygen tensions [6]. In support of this, bioluminescence imaging has been successfully applied in this fashion for the imaging of the tumor-colonizing anaerobic Bifidobacterium breve [122]. Also, high levels of Vibrio fischeri luciferase has been expressed in C. perfringens under strictly anaerobic conditions, thereby also providing confidence that the operon can be correctly expressed in a clostridial host [124, 125].
Clindamycin and Lincomycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and Eikenella corrodens are intrinsically resistant to clindamycin (Eick et al., 1999). Lastly, of 21 different antimicrobial agents tested, clindamycin and erythromycin had the greatest inhibitory effect on Gardnerella vaginalis, a microaerophilic Gram-negative to Gram-variable staining facultative anaerobic organism (McCarthy et al., 1979).
Alive attenuated Salmonella as a cargo shuttle for smart carrying of gold nanoparticles to tumour hypoxic regions
Published in Journal of Drug Targeting, 2019
Amirhosein Kefayat, Fatemeh Ghahremani, Hasan Motaghi, Soodabeh Rostami, Masoud A. Mehrgardi
Bacteria have a long history in solid tumours’ treatment [27]. Many researchers believe that bacteria can improve tumour drug delivery approaches because of their specific features like the selective targeting of hypoxic and anoxic regions as treatment-resistant regions [28,29]. Many kinds of bacteria have been utilised for the invading cancer cells and tumour shrinkage [30]. Also, bacteria can infect cancer cells and subsequently, activate the immune response against infected cancer cells which cause considerable immune system response against tumour [30]. Recently, bacteria have been applied to deliver various cytotoxic agents [31] or genes [32] to the tumour. Among various bacteria, attenuated strains of Salmonella offer many innate advantages over other bacteria and have been employed in many human clinical trials [33]. Salmonella is a motile facultative anaerobic organism and the anoxic and hypoxic niches of the tumour are its favourable sites for colonisation. It migrates toward the tumour and actively locates in these regions. Therefore, Salmonella as a tumour or even tumour hypoxic regions selective delivery vehicle has attracted lots of attention as a novel issue [34].
Influence of gut microbiota and intestinal barrier on enterogenic infection after liver transplantation
Published in Current Medical Research and Opinion, 2019
Jingzhou Mu, Qiuyu Chen, Liang Zhu, Yunhong Wu, Suping Liu, Yufei Zhao, Tonghui Ma
Intestinal opportunistic pathogens, such as Enterococcus, Enterobacter cloacae, and Escherichia coli, are the main causes of intestinal infections after liver transplantation. Intestinal bacterial translocation (BT) is the prime source of infections after liver transplantation. With the time-lapse of operation, infectious sites and pathogen distribution can be different. The main pathogen of early infections is Gram-negative bacteria, and infections always occur in the respiratory tract and abdominal cavity. After anti-infective therapy, susceptible groups are blood and bile duct. At this point, the major pathogens of infections are Enterococci, fungi, and E. cloacae, with a high yield of AmpC and ESBL enzymes29. These pathogens are dangerous and closely related to the death of patients after liver transplantation. Kim et al.30 observed bacterial infection in children, 57% of which occurred within 1 month after liver transplantation, whereas 99% occurred within 6 months. Among these infections, 55% are from Gram-negative bacteria, 44% from Gram-positive bacteria, and 1% from an anaerobic organism. The most common Gram-negative bacteria are intestinal bacteria, such as Klebsiella pneumoniae (12, 16%), Enterobacter faecium (7, 10%), E. coli (2, 3%), Citrobacters (2, 3%) and Enterobacter aerogenes (1, 1%). Thus, entergenous infections after liver transplantation are given priority.