Oxytetracycline and antisense oligonucleotides reduce titer and transmission of bacterial phytopathogen and improve health of citrus trees expressing Huanglongbing

Huanglongbing (HLB) is a systemic disease of citrus caused by the bacterial pathogen Candidatus Liberibacter asiaticus (CLas) that limits citrus production worldwide. There is no cure for HLB currently and broad-spectrum antibiotics represent one possible therapeutic against disease symptoms. Single-stranded nucleic acid analogs, 2’-deoxy-2’-Fluoro-β-D-arabinonucleic antisense oligonucleotides (FANA ASOs), can modulate gene expression by enzymatic degradation or steric blocking of an RNA target. Injection of oxytetracycline (OTC) into mature citrus trees with HLB ameliorated symptoms of disease, increased fruit yield, and quality of juice as compared with that produced by non-injected controls. Injection of trees with FANA ASOs also reduced CLas infection but did not improve fruit yield and quality above control levels at the injection dosage tested. Reduced pathogen titers following OTC or FANA ASO injection were coincident with lower CLas acquisition and inoculation. Trunk injection of OTC in rotation with antimicrobial technologies like FANA ASOs may be useful in management of HLB by reducing CLas infection in trees and disrupting transmission. Future investigations should prioritize optimizing FANA ASO dosage in trees and exploring the potential of multiplex FANA ASOs that simultaneously target multiple mRNAs to enhance efficacy against CLas infection.