AbstractBACKGROUNDAsian citrus psyllid, Diaphorina citri, is a notorious pest in the citrus industry because it transmits Candidatus Liberibacter asiaticus, which causes an uncurable, devastating disease in citrus worldwide. Serratia marcescens is widely distributed in various environments that exhibits toxic effects to many insects. To develop strategies for enhancing the efficiency of pathogen‐induced host mortality, a better understanding of the toxicity mechanism of Serratia marcescens on Diaphorina citri is critical.RESULTSSerratia marcescens KH‐001 successfully colonized Diaphorina citri gut by feeding artificial diets, resulting in the damage of cells including nucleus, mitochondria, vesicles, and microvilli. Oral ingestion of Serratia marcescens KH‐001 strongly induced apoptosis in gut cells by enhancing levels of Cyt c, p53 and caspase‐1 and decreasing levels of inhibitors of apoptosis (IAP) and Bax inhibitor‐1 (BI‐1). The expression of dual oxidase (Duox) and nitric oxide synthase (Nos) was up‐regulated by Serratia marcescens KH‐001, which increased hydrogen peroxide (H2O2) levels in the gut. Injection of abdomen of Diaphorina citri with H2O2 accelerated the death of the adults and induced apoptosis in the gut cells by activating Cyt c, p53 and caspase‐1 and suppressing IAP and BI‐1. Pretreatment of infected Diaphorina citri with vitamin c (Vc) increased the adult survival and diminished the apoptosis‐inducing effect.CONCLUSIONSThe colonization of Serratia marcescens KH‐001 in the guts of Diaphorina citri increased H2O2 accumulation, leading to severe changes and apoptosis in intestinal cells, which enhanced a higher mortality level of D. citr. This study identifies the underlying virulence mechanism of Serratia marcescens KH‐001 on Diaphorina citri that contributes to a widespread application in the integrated management of citrus psyllid. © 2023 Society of Chemical Industry.

Frontiers in MicrobiologyQ2 · BIOLOGY

Killing Effects of an Isolated Serratia marcescens KH-001 on Diaphorina citri via Lowering the Endosymbiont Numbers

Q2 · BIOLOGY

ArticleOA

Author: Lu, Zhanjun ; Kuang, Fan ; Hu, Wei ; Chen, Tingtao ; Zhang, Ning

Huanglongbing (HLB) is the most devastating citrus disease worldwide, and suppression of the Asian citrus psyllid (Diaphorina citri) is regarded as an effective method to inhibit the spread of HLB. In this study, we isolated a strain named as Serratia marcescens KH-001 from D. citri nymphs suffering from disease, and evaluated its killing effect on D. citri via toxicity test and effect on microbial community in D. citri using high-throughput sequencing. Our results indicated that S. marcescens KH-001 could effectively kill 83% of D. citri nymphs, while the fermentation products of S. marcescens KH-001 only killed 40% of the D. citrinymphs. High-throughput sequencing results indicated that the S. marcescens KH-001 increased the OTU numbers from 62.5 (PBS buffer) to 81.5, while significantly lowered the Shannon index compared with Escherichia coli DH5α (group E) (p < 0.05). OTU analysis showed that the S. marcescens KH-001 had significantly reduced the relative abundance of endosymbionts Wolbachia, Profftella, and Carsonella in group S compared with that in other groups (p < 0.05). Therefore, the direct killing effect of the fermentation products of S. marcescens KH-001 and the indirect effect via reducing the numbers of endosymbionts (Wolbachia, Profftella, and Carsonella) of D. citri endow S. marcescens KH-001 a sound killing effect on D. citri. Further work need to do before this strain is used as a sound biological control agents.

News (Medical) associated with KH-001(Kanna Health)

16 Nov 2023

·www.prnewswire.com

Kanna Health announces FDA and MHRA approvals to begin its Phase 1 clinical trial for the development of KH-001 as first FDA-approved treatment for premature ejaculation

LONDON, Nov. 16, 2023 /PRNewswire/ -- The US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) have approved Kanna Health's Investigational New Drug (IND) application and Clinical Trial Application (CTA), respectively, to start participant enrollment in a Phase 1 first-in-human clinical trial investigating the Safety and Pharmacokinetics of KH-001 Besylate (KH-001) in Healthy Male Subjects. KH-001 is a unique, proprietary on-demand drug being developed as the first FDA-approved treatment for premature ejaculation. These regulatory approvals signify a potential breakthrough in the management of a widespread condition, impacting up to 20% of men and their partners worldwide. The Phase 1 study will be conducted in the UK by Simbec-Orion, an experienced full-service Contract Research Organization (CRO). Dr Ryan Protzko, Kanna Health's President, stated: "Our clinical trial approval on both sides of the Atlantic represents a critical milestone as we officially become a clinical stage company. The study marks the start of a journey towards understanding the therapeutic potential of KH-001 in humans, in cooperation with regulatory bodies in our priority markets." "This approval allows Kanna Health to advance our understanding of how KH-001 may provide patients with a potentially transformative therapy, where no drug treatments are approved in the US and few treatment options exist worldwide", said Dr Hans-Juergen Gruss, Kanna Health's Chief Medical Officer. About Premature Ejaculation Premature ejaculation is the most common form of male sexual dysfunction, impacting ~20% of men (Shindel AW, Althof SE, Carrier S et al.: Disorders of Ejaculation: An AUA/SMSNA Guideline. J Urol 2022), with its most severe form characterized by ejaculation within 1 minute of penetration (~3% of men). Premature ejaculation is associated with secondary psychological effects, with 65% of patients reporting personal distress as a result including anxiety, depression, low self-esteem, and a negative impact on relationships. About Kanna Health Ltd Kanna Health is a clinical-stage biopharmaceutical company developing novel fast-acting small molecule therapeutics for sexual and mental health conditions. Further information: For further information, please contact John Boghossian (email: [email protected]). Logo -

Drug ApprovalPhase 1IND

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Indication	Highest Phase	Country/Location	Organization	Date
Premature Ejaculation	Phase 1	-	Kadence Bio Ltd.Startup	-

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