REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rat anti-AMA1	BEI Resources	MRA-897
Rabbit anti-P. berghei MSP1	Hanson Lab, UTSA	N/A
Chemicals, peptides, and recombinant proteins
Harzianin NPDG I	Cichewicz lab, University of Oklahoma; OU, USA	Ac-D-Iva-L-Gln-L-Leu-L-Ile-Aib-L-Pro-D-Iva-L-Leu-Aib-L-Pro-L-Leuol
Harzianin NPDG H	Cichewicz lab, University of Oklahoma; OU, USA	Ac-D-Iva-L-Gln-L-Leu-Aib-L-Pro-L-Ala-L-Ile-Aib-L-Pro-D-Iva-L-Leu-Aib-L-Pro-L-Leuol
Trichorzin HA II	Cichewicz lab, University of Oklahoma; OU, USA	Ac-Aib-Gly-L-Ala-Aib-Aib-L-Gln-Aib-L-Val-Aib-Gly-L-Leu-Aib-L-Pro-L-Leu-Aib-D-Iva-L-Gln-L-Leuol
L-Iva diastereomer of harzianin NPDG I	Cichewicz lab, University of Oklahoma; OU, USA	Ac-D-Iva-L-Gln-L-Leu-L-Ile-Aib-L-Pro-L-Iva-L-Leu-Aib-L-Pro-L-Leuol
L-Iva diastereomer of harzianin HB I	Cichewicz lab, University of Oklahoma; OU, USA	Ac-Aib-L-Asn-L-Leu-L-Ile-Aib-L-Pro-L-Iva-L-Leu-Aib-L-Pro-L-Leuol
Harzianin HB I – amide	Cichewicz lab, University of Oklahoma; OU, USA	Ac-Aib-L-Asn-L-Leu-L-Ile-Aib-L-Pro-D-Iva-L-Leu-Aib-L-Pro-L-Leu-NH2
Harzianin NPDG I – amide	Cichewicz lab, University of Oklahoma; OU, USA	Ac-D-Iva-L-Gln-L-Leu-L-Ile-Aib-L-Pro-D-Iva-L-Leu-Aib-L-Pro-L-Leu-NH2
Alamethicin	Abcam	Cat#ab141893; Ac-Aib-Pro-Aib-Ala-Aib-Ala-Gln-Aib-Val-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-Glu-Gln-Phl
SYBR Green I	Invitrogen	Cat#S7567
MTS reagent	Promega	Cat#PR-G3581
FITC-dextran	TCI America	Cat#F0918100MG
L-a-Phosphatidylcholine	Sigma-Aldrich	Cat#P3556-100MG
Hemin	Sigma-Aldrich	Cat#H9039-1G
YOYO-1	Invitrogen	Cat#Y3601
Paraformaldehyde	Sigma-Aldrich	Cat#P6148-500G
Anhydrotetracycline	Sigma-Aldrich	Cat#37919
Blasticidin S	RPI Corp	Cat#B12150–-0.1
2% Paraformaldehyde/2.5% Glutaraldehyde in 0.1M Sodium Cacodylate buffer	Electron Microscopy Sciences	Cat#15960-01
Cacodylate buffer	Electron Microscopy Sciences	Cat#11652
Mitotracker Deep Red FM	Invitrogen	Cat#M22426
Critical commercial assays
Direct-zol RNA MiniPrepPlus	Zymo Research	Cat#R2070
SuperScript First-Strand Synthesis System	Invitrogen	Cat#11904-018
SYBR Select Master Mix	Life Technologies	Cat#4472903
Renilla-Glo(R) Luciferase Assay System	Promega	Cat#E2750
Deposited data
Harzianin NPDG I-selected resistance line sequencing	NCBI Sequence Read Archive	Accession #PRJNA812929
Harzianin NPDG I-RNASeq Data	NCBI Sequence Read Archive	Accession #PRJNA1018932
Experimental models: Cell lines
Parasite line 3D7	BEI Resources, MRA-102	N/A
Parasite line Dd2 (Chakrabarti Lab)	BEI Resources, MRA-150	N/A
Parasite line Dd2 B2 (Winzeler lab)	PMID: 29326268	N/A
Parasite line PfACS_A597	PMID: 34348113 gifted via the David Fidock lab	N/A
Parasite line PfCARL_I1339K	PMID: 27381290	N/A
Dd2-ScDHODH	Transgenic parasite line expressing Saccharomyces cerevisiae dihydroorotate dehydrogenase, PMID: 17330044	N/A
Parasite line PfPI4K_S1320L	PMID: 24284631	N/A
PbLuc, Parasite line P. berghei-ANKA-GFP-Luc-SMCON	Insectary Core Facility, New York University	N/A
PfMDR1 cKD Parasite line	Niles Lab	N/A
Parasite Line NF54	Niles Lab	N/A
Human hepatocyte line HepG2 (Chakrabarti Lab)	ATCC HB-8065	N/A
Human hepatocyte line HepG2 (Winzeler lab)	ATCC HB-8065	N/A
Human hepatoma HepG2 (Hanson lab)	STR profiled by ATCC to confirm identity (barcode STRA-1292)	N/A
Parasite line P. berghei ANKA 676m1cl1 (Hanson lab)	BEI Resources (MRA-868) for the UGA Sporocore	P. berghei ANKA
Experimental models: Organisms/strains
P. falciparum asexual blood stage parasites	BEI Resources, MRA-102	N/A
P. falciparum asexual blood stage parasites	BEI Resources, MRA-150	N/A
P. falciparum asexual blood stage parasites	Winzeler Lab	N/A
P. falciparum asexual blood stage parasites	Niles Lab	N/A
P. berghei liver stage parasites	Winzeler Lab	N/A
H. sapiens hepatocellular carcinoma cells	ATCC HB-8065	N/A
H. sapiens hepatocellular carcinoma cells	Winzeler Lab, HepG2-A16-CD81	N/A
Oligonucleotides
RT-qPCR primers	Listed in Table S5.	N/A
PfMDR1 RHR forward sequence	gtacggtacaaacccggaattcgagctcggGCAT TTATATGATCCGCAAA	N/A
PfMDR1 RHR reverse sequence	aagacgagagattgggtattagacctagggat aacagggtaatCCCATAT ATACTATACATATATATTATCATTTAG	N/A
PfMDR1 sgRNA target site	GGAACCTTTGTACAGTCACA	N/A
Recombinant DNA
pSN054	CRISPR donor vector, PMID: 33431920	N/A
LHR and re-codonized region (3736–4257 bp; stop codon removed)	ATGTTGGACCATATGGTAAAAGCTTA TCAGGTGGA CAAAAACAGAGAATAGCTATAGCT AGAGCATTATT AAGAGAACCTAAAATATTATTATTA GATGAAGCAA CATCATCACTTGATTCCAATTCTG AGAAATTAATT GAAAAAACTATTGTAGATATTAAA GATAAAGCTGA CAAAACTATTATTACTATTGCCCA CAGAATTGCAT CTATAAAACGATCAGACAAAATTG TGGTATTTAAT AACCCTGACAGAAATGGAACCTTC GTCCAGAGCCA CGGCACGCACGATGAATTGTTGTC TGCTCAGGACG GGATCTATAAGAAGTATGTGAAAC TGGCTAAA	N/A
Software and algorithms
GraphPad Prism Version 9	GraphPad Software; San Diego, CA, USA	www.graphpad.com
Cytoscape Version 3.91	Institute for Systems Biology; Washington, USA	http://cytoscape.org
FlowJo Version 10	Becton, Dickinson and Company; Ashland, OR, USA	www.flowjo.com
Biorender	Biorender; Toronto, Canada	https://biorender.com
CDD Vault	Collaborative Drug Discovery, Inc, Burlingham, CA, USA	https://www.collaborativedrug.com
Cutadapt	https://doi.org/10.14806/ej.17.1.200	https://cutadapt.readthedocs.io/en/stable/
FastQC	Andrews, S., FastQC: A Quality Control Tool for High Throughput Sequence Data. 2010.	https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
Bowtie2	Langmead B, Salzberg S. Fast gapped-read alignment with Bowtie 2. Nature Methods. 2012, 9:357-359.	https://bowtie-bio.sourceforge.net/bowtie2/index.shtml
HISAT2	https://doi.org/10.1101/gr.275193.120	http://daehwankimlab.github.io/hisat2/
StringTie	https://doi.org/10.1038/nbt.3122	https://ccb.jhu.edu/software/stringtie/#install
Gffcompare	https://doi.org/10.12688/f1000research.23297.1	https://ccb.jhu.edu/software/stringtie/gffcompare.shtml
edgeR	https://doi.org/10.1093/bioinformatics/btp616.	https://bioconductor.org/packages/release/bioc/html/edgeR.html
Instant Clue	https://doi.org/10.1038/s41598-018-31154-6	http://www.instantclue.uni-koeln.de/
Revigo	https://doi.org/10.1371/journal.pone.0021800	http://revigo.irb.hr/
PlasmoDB	The Plasmodium Genome Consortium (2001) PlasmoDB: an integrative database of the Plasmodium falciparum genome.	https://plasmodb.org/plasmo/app