ABSTRACT
Background: The World Health Organization (WHO) has classified carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa (P. aeruginosa), and Acinetobacter baumannii (A. baumannii) as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been reported to spread between humans, animals, and the environment. Objective: This study aimed to conduct a systematic review of carbapenem resistance in animals, foods, and the environment on the African continent and to provide recommendations and perspectives for better prevention and control of carbapenem resistance in Africa. Results: A total of 137 research articles collected from 2009 to 2023 were selected for this review, including articles reporting carbapenem-resistant bacteria in animals (81/137; 59.1%), the environment (66/137; 48.2%), and foods (26/137; 19%). Carbapenem-resistant bacterial species belonged to 31 genera and 17 families, including mainly Escherichia spp. (68/127; 53.5%); Klebsiella spp. (45/127; 35.4%); Pseudomonas spp. (20/127; 15.7%), Enterobacter spp. (19/127; 15%) and Acinetobacter spp. (15/127; 11.8%). The prevalence of CRBs by country ranged from 1.1% to 48.5%, and the pooled prevalence of CRBs isolated from animal-environment-food in Africa was 19.1% (2804/14,684; Standard Deviation = 15). Twenty carbapenemase families belonging to A, B, C, and D Ambler classes were reported, including mainly carbapenemase genes from blaOXA (44/84; 52.4%), blaNDM (34/84; 40.5%), blaSHV (23/84; 27.4%), blaKPC (22/84; 26.2%), blaVIM (19/84; 22.6%), and blaIMP (12/84; 14.3%) families. The reported mobile genetic elements (MGE) carrying carbapenemase-encoding genes included plasmids (16/19; 84.2%), integrons (3/19; 15.8%), transposons (3/19; 15.8%), and insertion sequences (2/19; 10.5%). blaOXA-48 was often carried by (60kb-65kb) IncL/M-type pOXA-48 plasmids, while blaNDM-5 was often carried by (45-50kb) IncX-type plasmids. Moreover, 25 articles investigated and reported virulent and hypervirulent CRBs that carried multiple virulence factors. Conclusion: Animal-environment-food ecosystems would constitute reservoirs of CRBs involved in human infections. The One Health approach and constant collaboration between governments are necessary to drastically reduce the mortality rates linked to antimicrobial resistance.
ABSTRACT
Drosophila Robo3 is a member of the evolutionarily conserved Roundabout (Robo) receptor family and one of three Drosophila Robo paralogs. During embryonic ventral nerve cord development, Robo3 does not participate in canonical Slit-dependent midline repulsion, but instead regulates the formation of longitudinal axon pathways at specific positions along the medial-lateral axis. Longitudinal axon guidance by Robo3 is hypothesized to be Slit dependent, but this has not been directly tested. Here we create a series of Robo3 variants in which the N-terminal Ig1 domain is deleted or modified, in order to characterize the functional importance of Ig1 and Slit binding for Robo3's axon guidance activity. We show that Robo3 requires its Ig1 domain for interaction with Slit and for proper axonal localization in embryonic neurons, but deleting Ig1 from Robo3 only partially disrupts longitudinal pathway formation. Robo3 variants with modified Ig1 domains that cannot bind Slit retain proper localization and fully rescue longitudinal axon guidance. Our results indicate that Robo3 guides longitudinal axons independently of Slit, and that sequences both within and outside of Ig1 contribute to this Slit-independent activity.
