While oxytetracycline has been used in agriculture for over 60 years, it is just one compound of a chemically diverse family of agents having variable activity across many different microbial species. Within this family, a select subgroup of compounds have discreet and targeted activity against alpha-proteobacteria, including CLas, the agent responsible for Huanglongbing (HLB), while devoid of activity against human bacterial pathogens. Such selectivity against HLB by these compounds can be used to treat plants while sparing the possibility of antibacterial resistance, creating microbial agents or biocides in their own class of compounds affecting HLB alone. Our efforts in tetracycline chemistry continue to produce the most highly active compounds found effective against the surrogate strain Liberibacter crescens (see http://citrusrdf.org/wp-content/uploads/2014/07/Antimicrobials.pdf), where most of the derivatives were 3 or more orders of magnitude more active than oxytetracycline. Two of the most potent compounds derived from these screening studies, designated EBI-601 and EBI-602, are being studied in models of phloem transport in citrus and were found to be transported throughout the plant by either foliar or bark application of the formulated compounds. In infected citrus trees both compounds showed the ability to suppress HLB (CLas) bacterial growth as determined by PCR levels as compared to infected control trees (studies ongoing), while leaves from HLB infected Valencia orange shoots showed significant repression of L10 and 16S mRNA levels, another indicator of HLB growth suppression and treatment. These results with both compounds show that chemically-modified tetracyclines are specifically active against alpha-proteobacteria and target HLB, decreasing the infection in whole citrus plants, without plant toxicity, and are considerably more active than currently used agents. Furthermore, these compounds have been described as some of the most potent compounds tested to date against HLB, and can be commercially produced in amounts needed to treat infected groves. Further compounds are being studied against the surrogate strain and in infected citrus, and as the chemical structure of the tetracycline is changed, major increases in activity against HLB are observed, describing the mechanisms by which tetracyclines can enter the plant and affect the bacterium while decreasing infectious disease symptoms. The ultimate goal of this study is to obtain the most suitable compound with highly potent anti-HLB activity, one with increased stability for field use, and to ensure its safety in the environment for registration through the EPA for use in agriculture. This study demonstrates for the first time that an effective and targeted microbicide can be chemically designed to combat agricultural diseases in commercially valuable crops.