Visceral leishmaniasis (VL) or Kala-azar, primarily caused by Leishmania donovani, is a major health concern in many countries including India. Growing unresponsiveness among the parasites toward the available drugs is alarming, and so, it is necessary to decipher the underlying mechanism of such development for designing new therapeutics. Moreover, even after successful treatment, some VL patients develop apparently harmless skin lesions known as post-kala-azar dermal leishmaniasis (PKDL) which may serve as a reservoir of the parasite in the transmission cycle. Furthermore, recent reports of para-kala-azar dermal leishmaniasis (para-KDL) cases having PKDL manifestation with concomitant VL, emphasize the necessity of more attention to address complex nature of the parasite for eradicating the disease effectively. In the present study, whole genome sequencing is performed with sodium stibogluconate (SSG) sensitive and resistant L. donovani strains along with SSG sensitive para-KDL strains, derived from the clinical isolates of Indian patients to identify the genomic variations among them. Notably, the analyses of chromosome somy values and genome wide mutation profile in the coding regions reveal distinct clustering of the para-KDL strains with 24 genes being mutated uniquely in this group. Such distinguishing genomic changes among the para-KDL strains could be significant for the parasites to become dermatotropic. Overall, the study reveals a possible correlation of the development of SSG resistance and the transition towards the manifestation of PKDL with chromosome aneuploidy and non-synonymous genetic variations in the coding sequences of the L. donovani strains from Indian patients.

内脏利什曼病 (VL) 或黑热病，主要由多诺瓦利什曼原虫引起，是包括印度在内的许多国家的主要健康问题。寄生虫对可用药物的反应越来越迟钝令人担忧，因此，有必要破译这种发展的潜在机制以设计新的治疗方法。此外，即使在成功治疗后，一些 VL 患者也会出现明显无害的皮肤病变，称为黑热病后皮肤利什曼病 (PKDL)，这可能是传播周期中寄生虫的储存库。此外，最近关于副黑热病皮肤利什曼病 (para-KDL) 病例具有 PKDL 表现并伴有 VL 的报告强调必须更加注意解决寄生虫的复杂性质以有效根除该疾病。在本研究中，全基因组测序是用葡萄糖酸锑钠 (SSG) 敏感和抗性进行的L. donovani菌株以及 SSG 敏感的 para-KDL 菌株，源自印度患者的临床分离株，以鉴定它们之间的基因组变异。值得注意的是，对编码区中染色体体值和全基因组突变谱的分析揭示了 para-KDL 菌株的不同聚类，其中 24 个基因在该组中发生了独特的突变。para-KDL 菌株之间的这种区分基因组变化可能对寄生虫变得亲肤性很重要。总体而言，该研究揭示了 SSG 抗性的发展和向 PKDL 表现的转变与来自印度患者的多诺瓦尼乳杆菌菌株编码序列中的染色体非整倍性和非同义遗传变异之间可能存在相关性。